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 Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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



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 National Institute on Deafness and Other Communication Disorders (NIDCD) at the National Institutes of Health (NIH) invites new, resubmission, revision or renewal applications for Clinical Research Center Grants (P50) in the mission areas of hearing, balance, smell, taste, voice, speech, or language. The P50 Clinical Research Center provides a vehicle for integrated, multidisciplinary approaches to critical clinical research questions that advance the study of prevention, pathogenesis, pathophysiology, diagnosis, treatment, management or epidemiology of a disease or disorder of hearing, balance, smell, taste, voice, speech, or language. The P50 provides an avenue for forming a multi-disciplinary team that is intended to bring innovative ideas and distinct perspectives to the generation and evaluation of high impact solutions to complex clinical problems. Responsive applications must include a multi-disciplinary team collaborating on a synergistic set of 3-4 research projects addressing a unifying theme. The synergistic and substantial integration of research projects is intended to generate breakthrough solutions to the unifying problem. The research efforts are further supported by an administrative core and 1-2 optional scientific cores to ensure rigorous and efficient progress towards the center’s unifying theme. Overall, the clinical research center provides a whole that will have impact beyond the sum of its parts.

Required Elements

Given the complexity of the P50 Clinical Research Centers, applicants are strongly encouraged to communicate with the scientific/research contact listed at the end of this funding opportunity for guidance on responsiveness to the following required elements. Applications that are not responsive or incomplete (e.g., are missing required elements) will be withdrawn and will not be reviewed.

To be responsive to this funding opportunity, a Clinical Research Center must include the following required conceptual and structural elements.

Clinical Research
For this funding opportunity, the research being conducted must have a clinical focus, usually defined as research involving individuals with sensory and/or communication disorders or data/tissues from individuals with a sensory and/or communication disorder. Examples include (but are not limited to) studies of the prevention, pathogenesis, pathophysiology, diagnosis, treatment, management or epidemiology of a disease or disorder of hearing, balance, smell, taste, voice, speech, or language. Although the intent is that all the research will involve individuals with sensory and/or communication disorders or data/tissues from individuals with sensory and/or communication disorders, when the clinical research goal(s) warrant(s) departures from this intent, alternatives are possible with appropriate and strong scientific justification and in consultation with NIDCD staff. In particular, studies with normal human subjects (e.g., those without a sensory or communication disorder) may be included in the research with appropriate justification that the inclusion of such data are essential for the clinical research goal(s) and/or the interpretation of the results (e.g., studies focusing on detection, diagnostic methods, or epidemiology). Likewise, for certain clinical research objectives (e.g., studies focusing on prevention), individuals at-risk for sensory and/or communication disorders may be included when strongly justified. Non-human research may be supported when the translational nature of the research is clearly articulated. Non-human research will be limited to (at most) one project. Across these alternative scenarios, there is an expectation that the majority of the research will focus on individuals with sensory and/or communication disorders and/or data/tissues from individuals with sensory and/or communication disorders.

Clinical trials, as defined by NIH, are optional. When a clinical trial is included, only low-risk clinical trials or Basic Science Experimental Studies involving Humans will be funded through this mechanism. Low-risk clinical trials: do not require FDA oversight, are not an NIH defined Phase III Clinical Trial, have low risks to subjects, and intend to gather scientific data/evidence to inform subsequent studies. This NOFO also supports Basic Science Experimental Studies involving Humans (https://grants.nih.gov/policy-and-compliance/policy-topics/clinical-trials/beshBESH). These studies fall within the NIH definition of a clinical trial and meet the definition of basic research. For more information about clinical trials at NIDCD, see https://www.nidcd.nih.gov/research/clinical-studies/researchers-professionals. 

Synergistic and Substantial Interaction around a Unifying Theme
The P50 Clinical Research Center Grant supports a research program in which an interdisciplinary team of investigators works on a clearly defined central theme of mutual scientific interest. This mechanism facilitates economy of effort, space, and equipment, and accelerates the acquisition of knowledge by stimulating collaboration among clinical investigators whose projects are directed toward a common goal. Each research project must be unambiguously related to the central unifying theme. The central unifying theme is a core idea, concept, problem, or question that ties together the research projects, creating a cohesive understanding and/or explanation that is greater than the sum of the individual projects. To achieve this cohesive understanding, synergistic and substantial interactions among the projects is required. That is, the P50 Clinical Research Center is not a collection of independent research projects on a topic but rather a fully integrated set of research questions and activities conducted by a collaborative, interactive research team. For example, measures or findings from one project could be leveraged in another project or could contribute to a larger integrative analysis across projects. Other examples are possible. In general, the integration and interaction is expected throughout all aspects of the Center’s work, from the conceptual (e.g., unifying theme) to the practical (e.g., research activities, researcher engagement).

Multidisciplinary
The overall P50 must provide multidisciplinary approaches to the central theme, defined as having research projects representing different disciplines, approaches and expertise.

Organization & Structure
A Center must be an identifiable, organizational unit with an administrative structure and clear lines of authority in order to facilitate coordination among Center personnel and to assure maximum accountability and efficiency in Center operations.

• Administrative Core (1 required). An Administrative Core is required. The lead of the Administrative Core is also the Director of the Center who is responsible for the organization and overall operation of the Center.
•  
• Scientific Cores (1-2 optional). The P50 may include 1-2 scientific cores. Cores are not required or essential criteria. Scientific Cores (when included) provide infrastructure/support for commonly needed resources or services required by multiple projects. Examples of scientific cores include patient management, data management, or technical support (e.g., speech processing, neuroimaging, statistics, genomics). When included, a core must serve at least two or more projects. Requests must be carefully justified and not be used to acquire additional support that duplicates existing resources already at the institution. Although the primary goal of the scientific cores is to support the research activity in the research projects, it may be appropriate for scientific cores to contribute to a broader scientific community by disseminating best practices in their area of infrastructure/support through websites, white papers, research notes, or methods papers. Such dissemination activities are of secondary importance and should not detract from their primary role of providing critical support to facilitate the aims of the research projects. 
• Research Projects (3-4 required). The P50 must have three to four research projects centered on a well-defined unifying theme. The primary research activity is to be conducted in the research projects.
   

External Advisory Committee
Each proposed Center must have an external advisory committee. The external advisory committee will provide oversight of scientific progress of the Center and guide the research plan when appropriate. Members of the external advisory committee should not be named in new applications. Refer to Section IV. Application and Submission Information for details.
 

Consultation with NIDCD Staff Highly Encouraged Prior to Application

Given the complexities of the P50 Clinical Centers, prospective applicants are strongly encouraged to communicate with the scientific/research contact listed at the end of this funding opportunity as early as possible to discuss how their application will incorporate all required elements. Pre-application consultation is particularly critical when proposing a clinical trial and/or when pursuing elements requiring strong justification (as noted above in the required elements section). 

Non-Responsive Applications

The following applications will be considered non-responsive for this funding opportunity and will not be reviewed:

• Applications outside NIDCD mission areas
• Applications where the majority of the research does not focus on individuals with sensory and/or communication disorders and/or data/tissue from individuals with sensory and/or communication disorders
• Applications that include clinical trials entailing greater than low-risk
• Applications that do not have synergistic and substantial interaction around a unifying theme
• Applications that are not multidisciplinary
• Applications that have a scientific core or cores used by only one research project
• Applications that do not describe an external advisory committee in terms of general expertise and planned activities

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

Foreign Organizations/ International Collaborations

NIH will no longer issue awards (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. This new requirement was effective, May 1, 2025.

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.

Non-domestic (non-U.S.) Entities (Foreign Organization) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the 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.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • 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 registration; 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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. 

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- Definitions 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 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Renewal applications:

Renewals must be submitted only after a minimum of 4 years of the project have been completed. Applications submitted before 4 years of funding have been completed will be withdrawn and not reviewed.

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 or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application.

Revision applications must include an Overall component and the components that are affected by the revision. Therefore, the component requirements listed below may not apply to the revision application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Scientific Cores: optional (0-2)
• Projects: required (3-4)

External Advisory Committee

For new applications and resubmission of a new application, in order not to restrict the pool of available scientific peer reviewers, you should not invite or name in your application potential members of your External Advisory Committee.

Overall Component

When preparing the application, use Component Type ‘Overall’.

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.

Specific Aims: Specific Aims are required. Provide an overview of the entire research program and describe the defined central theme and goals of the Clinical Research Center (P50). Provide the rationale for the proposed research program. Include potential impact, any areas of special interest, and any research ideas, disease entities, and target populations to be studied. Explain the research plan for achieving the objective(s) of the overall research program and how each research project and core relates to that overall plan.

Research Strategy: Explain how this Clinical Research Center Grant (P50) application supports an investigator-initiated research program in which a multidisciplinary team of investigators works in a clearly defined central theme of mutual scientific interest. Describe how this effort facilitates economy of effort, space, and equipment, and accelerates the acquisition of knowledge by stimulating cooperation among clinical investigators whose projects are directed toward a common goal. Describe how this overall Research Center will provide a whole that will have an impact beyond simply the sum of its parts. Describe how the research focuses on individuals with sensory and/or communication disorders or data/tissues from individuals with a sensory and/or communication disorder. Indicate any prior collaborative arrangements between investigators in the group; emphasizing the events that led to the current application; predict the anticipated advantages that would be gained by including the research in the proposed program; describe the overall theme of the Center and how research subprojects are related to the theme; and describe the multidisciplinary nature of the proposed research.

Letters of Support: Include any letters of support for the proposed Center by appropriate institutional officials of each performance site. These letters should include commitments of space and other resources required by the Center. A letter of agreement from existing resources (such as the CTSA PD(s)/PI(s)) should be included here if collaborative linkages are being developed between the Center and the existing resources.

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:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form (Overall)

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

Administrative Core (Required)

When preparing your application, use Component Type ‘Administrative Core’.

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

SF424 (R&R) Cover (Administrative Core)
Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)
Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)
Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

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

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)
List all performance sites that apply to the specific component.

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

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

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

Budget (Administrative Core)
Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe how the Administrative Core administration will coordinate and manage activities across the components of the Research Center.

Research Strategy: Describe the organizational framework for the management, direction and coordination of the Center to ensure that all proposed components and related activities will function in an optimal and synergistic manner. Include information on how this core will facilitate administration of the budget. This core should be described in sufficient detail to assure that all proposed components and related activities will function optimally. In addition, day-to-day operations involving procurement, finances, personnel, planning, and budgeting should be detailed in the description of this core.

Describe how the Administrative Core will enhance the overall research of the Center. The PD/PI provides scientific and administrative leadership for the Center, so the PD/PI must have a demonstrated ability to coordinate, integrate, and provide guidance in establishing multi-faceted research programs. Describe the administrative framework to manage the Research Center and each core, including the roles of the Research Center/Administrative Core Director and Research Projects and Scientific Core Directors, the lines of authority and relationship to appropriate institutional officials, how access and utilization of services will be prioritized, how potential disputes will be resolved, and how periodic evaluations will be used to improve the services. Describe how the proposed Administrative Core will foster close interactions among the various component Directors and other appropriate institutional administrative personnel.

The External Advisory Committee should be actively involved in the evaluation and planning process of the Center. New and resubmission of new applications should not name members of the external advisory committee but rather should describe the general composition of the committee in terms of number of members and types of expertise and the planned activities of the committee. Members of the external advisory committee will be named during the award process. Renewal applications and resubmission of renewal applications must name current members of the external advisory committee, if those members plan to continue to serve on the committee during the renewal period. The External Advisory Committee should meet formally at least annually to assist the Center Directors in evaluating the scientific progress and optimizing strategies to meet its overall research goals over the course of the grant award. 

Letters of Support: Provide letters of support from outside consultants as needed. For new applications and resubmission of a new application, do not include letters for External Advisory Committee members as they will be named after an award is made. If these documents are included in the Overall component, please state so.

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: 

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:
Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

Scientific Core (Optional)

When preparing your application, use Component Type ‘Core’.

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

SF424 (R&R) Cover (Scientific Core)
Complete only the following fields:

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

PHS 398 Cover Page Supplement (Scientific Core)
Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific Core)
Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

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

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Scientific Core)
List all performance sites that apply to the specific component.

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

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

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

Budget (Scientific Core)
Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Scientific Core)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: Specific aims are required. Concisely describe how this Scientific Core will provide services to the various components in the Clinical Research Center. Describe how the scientific core will increase effectiveness by sharing expertise or centralizing labor-intensive tasks, how it will encourage and facilitate collaborative work, or promote public health advances. Research activity is to be conducted in the research projects and not in the cores; the cores are to serve as infastructure/support.

Research Strategy: Describe the services and resources to be provided to investigators. The description should include a discussion of the core's contributions to the research objectives of the Center. Relevant aspects of cost-effectiveness, time-saving, and increased efficiency attributable to the existence of the cores should also be addressed. A core component should support two or more of the Center’s scientific research components.

Describe how the Scientific Core facilities or services will enhance research activities of the Clinical Research Center using this core, and add benefits to the research accomplishments; include the required significance, innovation and approach. Include how the Scientific Core will provide increased or innovative capabilities; facilitate increased productivity or effectiveness through sharing expertise or centralizing labor-intensive tasks; and/or foster collaborative or new research directions or attracting new investigators into an area. Describe each proposed technique or service in the Scientific Core, and its current status of staffing, space and equipment, in enough detail to allow a comprehensive evaluation. Describe briefly existing methodologies already in use at the institution; describe in more detail methodologies new to the institution with strategies for their successful implementation. Include any developmental methods for research or training, if proposed. If applicable, include sections on quality control. The ability to articulate user benefit is a critical factor in review. Include plans for administration, organization and proposed management of the individual Scientific Core.

Include plans to implement core services, to prioritize investigator use among projects competing for core use, and to resolve potential disputes. If the core is used to train investigators in special techniques, describe the nature and extent of this training and the qualifications of core personnel to provide and oversee this training. Any plans for disseminating best practices to center investigators or the broader research community (e.g., websites, white papers, research notes, or methods papers) should be described. In addition, plans for ensuring that these dissemination activities do not detract from the scientific core's primary role in providing critical support to facilitate the aims of the research projects must be described.

Discuss the potential for budgetary overlap, whether minimal or extensive, between the Research Projects and the Scientific Core, including personnel effort as well as other categories. If appropriate, provide a strategy for reimbursement of core services. Describe the investigator and his/her established expertise relevant to the support or service to be provided.

Letters of Support: Provide letters of support from outside consultants as needed. If these documents are included in the Overall component, please state so.

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:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.
   

Appendix:
Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Scientific Core)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the How to Apply- Application Guide must be followed.


Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.
 

Research Project

When preparing your application, use Component Type ‘Project’.

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

SF424 (R&R) Cover (Research Project)
Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Project)
Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)
Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

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

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Project)
List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Research Project)

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

Budget (Research Project)
Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project)
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: The specific aims should provide a clear description of the major goals and objectives of the project and how it integrates with the other research components in relation to the overall Center program’s central theme. The hypotheses to be tested should be focused and fully detailed.

Research Strategy: The design and procedure should describe the strategies proposed to accomplish the specific aims and the innovative aspects of the approach should be highlighted. A description of the resources and working arrangements required to implement and conduct the proposed research should be fully elaborated with particular attention to a description of necessary resources, subjects, clinical populations, tissue resources, biological models, existing data sets, etc. in the proposed studies. The application should describe the project's Significance, Approach, and Innovation in sufficient detail for evaluation by reviewers. The research strategy should describe how the project goals and objectives integrated with the other research components and contribute to the Center's unifying theme.

Letters of Support: Provide letters of support from outside consultants as needed. If these documents are included in the Overall component, please state so.

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:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:
Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Project)
When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

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) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. 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 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.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit 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) and component Project Leads 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.

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 How to Apply - Application Guide. 

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

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 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 Clinical Research Center 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).

In arriving at an overall impact score for the Research Center, reviewers will consider the impact scores from the individual projects and the ratings from the cores. In addition, reviewers will consider the following criteria:

• How does the Research Center provide a whole that will have an impact beyond simply the sum of its parts?
• What are the benefit(s) of combining the multi-components (research projects/cores) to form a Center?
• How cohesive are the projects of the Center, with respect to their interrelationship and coordination?
• How does the collaboration among research team members contribute to the success of the Center and assure a cohesive program? 

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?

Additional Review Criteria - Overall

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

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Human Subjects Policies

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for inclusion. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research. 

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the American Veterinary Medicine Association (AVMA) Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

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

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations - Overall

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

Review Criteria for Individual Research Projects within the Center

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.

Overall Impact - Project
Reviewers must provide an overall impact score for each individual project 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 - Project
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?

In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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

In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and
2) inclusion (or exclusion) of individuals on the basis of sex, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
In addition, for applications involving clinical trials
Does the application adequately address the following, if applicable

Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
 

Review Criteria for Cores within the Center

The primary research activity is to be conducted in the research projects. An Administrative Core is required to provide organization and facilitate the overall operation of the Center. Scientific Cores (1-2) are optional. Scientific Cores (when included) provide infrastructure/support for commonly needed resources or services required by two or more projects. Scientific Cores are evaluated based on how well they provide the needed infrastructure/support for common resources or services. Cores may disseminate best practices to center investigators and/or the broader scientific community, but this is optional and should not detract from their primary role of providing critical support to the research projects. As applicable for the core proposed, reviewers will evaluate the following additional items while determining scientific and technical merit. Reviewers will not give separate evaluation for each item noted, but rather, will provide an overall assessment of how well the core contributes to the success of the center. Reviewers will select one of two assessment categories: the core provides acceptable support (i.e., strengths balance or outweigh weaknesses) or the core provides unacceptable support (i.e., weaknesses outweigh strengths). 
 

Administrative Core
How well described is the Administrative Core and the short- and long-term goals and metrics that will be used to assess progress? How well described is the proposed structure? How clear are the roles of the PD(s)/PI(s) and any other committees? How appropriate are the plans for allocating and prioritizing fiscal and other resources and ensuring good communication across all Center components? How well described are the approaches, criteria and plans to measure, monitor, track and evaluate the progress and performance of all project activities and how adequate are these approaches, criteria, and plans for assessing progress/performance? Overall, how well does the administrative core contribute to the success of the center? Select from the following two options: provides acceptable support (i.e., strengths balance or outweigh weaknesses) or provides unacceptable support (i.e., weaknesses outweigh strengths).

Scientific Core(s)
How well does the application describe the scientific rationale and process used to select the proposed scientific core, as well as plans and procedures to monitor and assess progress? How well do the shared core facilities support two or more projects of the proposed research activities? How feasible and clear are the plans for prioritizing the use of shared facilities, for allocating availability to proposed research projects, and for ensuring they are used to the fullest extent, including access by non-Research Center investigators and institutions? How appropriate are the qualifications, experience and commitment of key personnel for running the core facilities/activities? How well documented is the need for the proposed scientific cores in the context of existing facilities in the applicant institution and region? If the core is engaging in dissemination activities, how appropriate are these activities and how do they enhance or detract from the cores primary role of supporting the research projects? Overall, how well does the scientific core contribute to the success of the center? Select from the following two options: provides acceptable support (i.e., strengths balance or outweigh weaknesses) or provides unacceptable support (i.e., weaknesses outweigh strengths).

Additional Review Criteria – Projects, Cores

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

Study Timeline
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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

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

Inclusion of Human Subjects Policies

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for inclusion. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.  

Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

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

Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

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

Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations - Projects, Cores

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.

Applications from Foreign Organizations
Not Applicable

Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans
Reviewers will comment on whether the Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

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 NIDCD Advisory Council. The following will be considered in making funding decisions:

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

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 their 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: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the 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.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.

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:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and
2. 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.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. 

• 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)

Finding Help Online: https://www.era.nih.gov/need-help  (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Holly L. Storkel, Ph.D.
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: (301) 496-5061 
Email: [email protected]

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

Samantha Tempchin
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-435-1404
Email: [email protected] 

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.