EXPIRED
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Eye Institute (NEI)
National Human Genome Research Institute (NHGRI)
National Institute on Aging (NIA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
U01 Research Project Cooperative Agreements
Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
The purpose of this Notice of Funding Opportunity is to solicit applications for clinical sites that will provide expert diagnostic services for undiagnosed diseases across the nation. The clinical sites known as Diagnostic Centers of Excellence (DCoEs) will partner with the Undiagnosed Diseases Network (UDN) to sustain some of the key research activities currently performed by the Phase II UDN Clinical sites (see:RFA-RM-17-019) and facilitate its transition to a larger network that serves undiagnosed patient populations including minority health and other populations defined by the NIH to experience health disparities. The DCoEs will establish collaborations and efficient processes with the Data Management and Coordinating Center (DMCC; see: RFA-NS-22-051); enroll and evaluate new participants; and foster scientific discovery.
This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn.
Applicants are strongly encouraged to read the FOA instructions carefully and view the available PEDP guidance material.
30 days prior to the application due date
Application Due Dates | Review and Award Cycles | ||||
---|---|---|---|---|---|
New | Renewal / Resubmission / Revision (as allowed) | AIDS - New/Renewal/Resubmission/Revision, as allowed | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
November 03, 2023 | November 03, 2023 | Not Applicable | March 2024 | May 2024 | July 2024 |
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.
No late applications will be accepted for this Notice of Funding Opportunity (NOFO).
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Background
Undiagnosed diseases are defined as long-standing symptoms or elusive medical conditions that have not been diagnosed despite extensive clinical evaluation. Undiagnosed diseases are often due to rare conditions and can include: 1) previously described diseases that are not recognized due to very low incidence or prevalence; 2) yet-to-be-described disorders that have not been previously documented; and 3) rare variations of more common diseases. These conditions and the lack of a diagnosis present difficult problems for patients, their families, and physicians resulting in a high emotional, physical, and financial burden to patients who may spend many years seeking a diagnosis and path to treatment. Diagnoses in these difficult cases require teams of clinicians and scientists with a wide variety of special expertise. Scientific advances springing from these diagnoses require an organized approach to testing, data analysis, and validation in patients with similar rare conditions or in model organisms.
In 2008, the NIH established an intramural Undiagnosed Diseases Program (UDP) to aid individuals plagued by longstanding medical conditions that elude medical diagnosis. Using a team science approach, comprehensive clinical phenotyping and cutting-edge diagnostic and genomic technologies, the UDP was successful in ending the diagnostic odyssey for many individuals with rare, challenging, and difficult-to-diagnose diseases. Based on the success of the UDP, the NIH Common Fund announced in 2012 an expansion of the UDP to form a nation-wide network - the Undiagnosed Diseases Network (UDN) - composed of the NIH UDP and extramural Clinical Sites. Phase I (FY2013-2017) of the UDN included seven Clinical Sites including the UDP, a Coordinating Center, and Core Laboratories to facilitate diagnoses (genome sequencing, testing variants in model organisms, metabolomics, and a biorepository). In Phase II (FY2018-2022), the number of Clinical Sites was expanded to twelve.
Over the past decade, the UDN has been very successful in achieving its objectives. Notably, through team science and collaboration, UDN investigators have provided difficult diagnoses for more than 650 individuals and discovered hundreds of novel disease-associated genes and genomic variants, including the identification of new diseases and syndromes. Together, the UDN has built an international reputation for advancing disease research while establishing exemplary clinical practices for undiagnosed diseases.
The UDN transitioned from the Common Fund in July 2023 and is currently administered by 17 different NIH Institutes and Centers along with the NIH Office of the Director. To have a broader impact on the clinical practice of undiagnosed diseases in the United States (US), the NIH envisions the UDN evolving into a larger, self-sustained network that, with public and private partners, can provide expert diagnostic services for undiagnosed patients across the nation and foster scientific discovery. In addition, the next phase of the UDN seeks to expand access to individuals and groups who historically have not benefited from modern diagnostic investigations (e.g., individuals from minority health and other populations defined by the NIH to experience health disparities). Leveraging the knowledge gained from the Phase I/II UDN (also see: Manual of Operations), the Phase III Network consists of a Data Management and Coordinating Center (DMCC), highly qualified and collaborative clinical sites including the UDP [referred to as Diagnostic Centers of Excellence (DCoEs)], patients with undiagnosed diseases (referred to as participants in this NOFO), family members, patient advocacy groups, the NIH and other stakeholders including external funding providers and/or resource providers (e.g., research cores administered by the DMCC). The NIH anticipates expanding the number of U01 Clinical Sites in Phase III (e.g., 12-15).
The overarching goals of the UDN in Phase III include:
Purpose and Research Objectives
The purpose of this NOFO is to solicit proposals from highly qualified clinical sites in the US to join the Phase III Network as DCoEs through a U01 Cooperative Agreement award. Awarded DCoEs will have access to DMCC resources and infrastructure including high-quality phenotypic and genotypic data and collaboration with highly skilled physicians, researchers, and bioinformaticians. Successful applicants will demonstrate that they have the appropriate expertise, resources and infrastructure needed to conduct advanced diagnostic evaluations at their site and propose a research plan that meets the following Phase III priorities:
Additional information
Successful applicants will be required to use a single-IRB managed by the NIH UDP that is consistent with NIH’s Single IRB Policy as described in NOT-OD-16-094 to ethically review Network-wide protocols involving human subjects research.
Plan for Enhancing Diverse Perspectives (PEDP)
Rigor and Transparency
NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance to the scientific community (https://www.ninds.nih.gov/Funding/grant_policy). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.
Program Formation and Governance
The awards funded under this NOFO will be cooperative agreements (see Section VI for Cooperative Agreement Terms and Conditions of Award). Because this is a cooperative agreement, extensive collaboration and management input from the NIH will occur regarding DCoE activities. The DCoE will be expected to propose measurable milestones and timelines in the application which will be used to assess progress and in consideration for funding of non-competing award years. To ensure that NIH’s investment in the DCoE is valuable, the NIH may negotiate and revise the milestones at the time of the award (e.g., by requiring a minimum number of participants to enroll each year and measurable research outcomes).
Network governance is the same as described in RFA-NS-22-051, and will be managed by the Steering Committee, with advice from an External Advisory Committee. The Network Steering Committee (voting members defined below) will identify scientific and policy issues that need to be addressed at the network level, as well as broad issues in the field of rare, undiagnosed diseases research that can be addressed by the Network. It will also ensure dissemination of undiagnosed diseases clinical practice and research knowledge to the wider scientific community, which includes sharing de-identified participant data. The Steering Committee may establish subcommittees and working groups to facilitate development, implementation, and monitoring of specific Network functions as needed.
The External Advisory Committee will be named by the NIH and the Steering Committee, and will serve in an advisory capacity by reviewing network activities and making recommendations to the Steering Committee, the NIH and other stakeholders regarding process and substantive issues that arise during network operations.
The Network Steering Committee will be composed of the following voting members:
Data Sharing under this Initiative
To increase the value of the significant public investment in the creation and operation of the Network, data from the Network are expected to be well managed and broadly shared in a timely manner. Consistent with achieving the goals of the program, NIH expects that the project datasets (phenotypic, genomic, environmental, covariates, and other relevant data and metadata) will be widely shared with the scientific community for research, while carefully observing standards of patient privacy, confidentiality, and management of health information in compliance with local, international, and federal regulations. Recipients must comply with the NIH Data Management and Sharing Policy and the NIH Genomic Data Sharing Policy. Working with the DMCC, controlled-access data must be registered in dbGaP and deposited into the AnVIL. Plans for data sharing are also expected to address data sharing sustainability and maintenance after the award ends. Applicants are also expected to collaborate with the Network Steering Committee to develop and implement future network-wide guidelines for data deposition as the need arises.
Resource Sharing under this Initiative
Resources generated by the DCoEs are also expected to be widely shared within the Network and with the broader scientific community for research as appropriate considering patient confidentiality. The Network Steering Committee will develop and implement network-wide approaches for resource deposition and use including submission to national repositories as appropriate.
Interim and Final Reports
Applicants are expected to participate with the DMCC in preparing interim or a final report for the NIH, External Advisory Committee, and other key stakeholders, as needed.
Applications Not Responsive to this NOFO:
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.
Not Allowed: Only accepting applications that do not propose clinical trials.
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budgets may not exceed $500,000 Direct Costs per year and must reflect the actual needs of the proposed project. Budgets may be administratively reduced before award based on program priorities and the amount of NIH appropriations.
The maximum project period is 4 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.
1. Eligible Applicants
All organizations administering an eligible parent award may apply for a supplement under this NOFO.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Government
Other
Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
Applications for this DCoE U01 NOFO (RFA-NS-24-008) may be submitted by individuals located at the same institution(s) as the DMCC award (see RFA-NS-22-051), but an individual may not be the PD/PI of both the DMCC award and a DCoE application. Institutions/organizations and PD/PIs are allowed only one DCoE award that is active at the same time [e.g., under this NOFO (i.e., RFA-NS-24-008), PAR-NS-23-171 or RFA-NS-23-004]. Therefore, recipients and PD/PIs of an approved X01 access award under PAR-23-171 may submit an application under this NOFO but will be required to relinquish the X01 access award if this U01 is awarded. Likewise, if recipients of a U01 award under RFA-NS-23-004 submit a New application under this NOFO, versus a Renewal application, they will be required to relinquish the original grant if a new U01 is awarded.
2. Cost Sharing
This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement.
3. Additional Information on Eligibility
Number of Applications
Only one application per institution (normally identified by having a unique UEI or NIH IPF number) is allowed.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Argenia Doss
Telephone: 301-827-6369
Email: argenia.doss@nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources:
In addition to the information required in the standard instructions, applicants should describe the relevant institutional facilities, equipment, resources and services that can be leveraged for accomplishing the specific goals of the proposed program and Network (e.g., clinical and laboratory facilities, diagnostic equipment, informatics/computational platforms, data storage and security resources, consultative and statistical resources, communication platforms, etc.).
Other Attachments: Applicants must provide the following additional materials in support of their application. The attachments must be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks). Applications that do not include these attachments will be considered incomplete and will not be reviewed.
Attachment 1 (Required - 1 page maximum; use file name External Sources of Support ):
As described in Section I. Funding Opportunity Description, applicants are expected to seek reimbursement from outside funding sources for patient services and routine diagnostic testing (e.g., by billing insurance, utilizing support from their institutions, outside partnerships, state and federal grants, philanthropic organizations, foundations, or private donors). Describe existing or planned resources available to applicant (in addition to the costs budgeted in this application) and an overview of how these resources will be leveraged to cover the patient costs and diagnostic testing of UDN participants at the site. Describe and justify which patient costs are not reimbursable through insurance or outside partnerships at the site and thus require NIH funds, including whether NIH funds will be prioritized to cover patient costs or travel expenses for economically disadvantaged participants and/or those who are under/uninsured.
Attachment 2 (Required 1 page maximum; use file name Plan for Enhancing Diverse Perspectives ):
All applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity using the following guidelines:
Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:
Applications that do not include these attachments will be considered non-compliant and will not move forward in review.
All instructions in the SF424 (R&R) Application Guide must be followed.
Address the following elements in the relevant Biographical Sketches (and as appropriate):
At least one PD(s)/PI(s) must devote a minimum of 2.4 person months (20% of full-time professional effort) to this Program.
All instructions in the SF424 (R&R) Application Guide must be followed.
Clinical services, routine testing and sequencing costs for Network participants should be billed to insurance when allowed. However, DCoEs must also prioritize and plan for economically disadvantaged participants who are under/uninsured and should include these costs in their budgets if justified and not reimbursable by billing insurance or through outside partnerships. Include costs to support the travel, room and board for economically disadvantaged Network participants, if needed and not covered by outside partnerships.
In the budget justification: include an estimate of the number participants the DCoE expects to enroll who are insured vs. under/uninsured, and the per-patient costs to conduct the clinical evaluation and sequencing (if indicated) in each case.
Do not include costs associated with research-grade testing or sequencing (e.g., Whole Genome Sequencing, RNA sequencing, metabolomics, immunologic profiling, etc.) and other research activities (e.g., gene function studies in model organisms or cell-based assays) that can be supported through DMCC-supported research cores or subawards issued by the DMCC (see: RFA-NS-22-051 for details).
Budgets should include any funds required to support sharing of scientific data under this NOFO. Investigators whose research projects are also subject to the Genomic Data Sharing (GDS) Policy should also include requested costs for genomic data management and sharing (e.g., obtaining samples with explicit informed consent for future research use and broad data sharing, implementing processes to seek new consent from study participants, etc.). The Budgeting for Data Management Sharing webpage provides guidance on costs that may be requested in an application for funding.
PEDP implementation costs
Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm) including but not limited to resources needed by the community collaborators (as described in Section I. Funding Opportunity Description).
R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims
List each aim for the DCoE and how it supports the Objectives of this Research Program as described in Section I. Funding Opportunity Description.
Research Strategy
This NOFO urges investigators to follow the NIH guidance for rigor and transparency in grant applications (https://grants.nih.gov/policy/reproducibility/guidance.htm) and additionally recommends the research practices described at https://www.ninds.nih.gov/Funding/grant_policy.
Describe the overall strategy, methodology, and analysis to be used to accomplish the specific aims of the project, including a description of:
Expanding access to the UDN for minority health and other populations defined by the NIH to experience health disparities is a top priority in the Phase III UDN. Applicants are required to address the following:
Integration and collaboration are essential tasks for DCoEs and other UDN members. Applicants are required to describe the following:
Bioinformatics Plan
Propose a plan for bioinformatics analysis to include:
Assessment, Dissemination, and Outreach
Propose a plan for assessment, dissemination, outreach, and training to include:
Letters of Support: Applicants should provide letters of support that indicate their willingness to participate in a network that uses a single IRB to review Network-wide research protocols. Institutional commitments to support DCoE functions both in this award and beyond NIH grant support should be clearly documented. Letters should also be included that reflect any additional resources and partnerships (e.g., relevant patient advocacy groups and other health interest groups, non-profits, foundations, industry partners or philanthropic organizations, etc.) that will be utilized to achieve the goals of the DCoE. Applicants should also include letters from their community collaborator(s) clearly outlining how they will partner with the applicant to achieve the goals of the program.
Resource Sharing Plan:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
NINDS is committed to the timely release of open-source software, and sharing of reagents including model organisms, cell lines and tools developed from proposed studies. It is expected that the DCoEs will work closely with the DMCC and Network members to ensure that resources such as but not limited to model organisms, cell lines, study protocols, descriptions, bioinformatics tools, and publications are made available to the public through public repositories, open access databases, public websites, etc. Applicants should describe in the Resource Sharing Plan a plan for open dissemination of software and other research tools to the community such that they are readily usable and extensible, where applicable.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.
The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NINDS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Prior Consultation with Scientific/Research Staff
Consultation with relevant NIH Scientific/Research staff is strongly encouraged, not later than the Letter of Intent due date. This is not the same as the Letter of Intent and should be included as a separate communication to the Scientific/Research Contacts (see Section VII). If requested by the applicants, staff can advise whether the proposed project meets the goals of this NOFO and the mission of NINDS and discuss responsiveness questions. Staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this NOFO. During the consultation phase, if the proposed project does not meet the programmatic needs of this NOFO, applicants will be strongly encouraged to consider other Funding Opportunities.
Applicants are required to follow the instructions for post-submission materials, as described in the policy
1. Criteria
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For Renewal applications (i.e., recipients of an award under RFA-NS-23-004), note the following: Reviewers may consider prior progress and productivity from the applicant’s previous UDN awards, and whether recruitment milestones were met.
Overall Impact
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this NOFO:
To what extent will this project significantly contribute to:
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?
Specific to this NOFO:
How well do the PD(s)/PI(s) and research team demonstrate that they have:
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?
Specific to this NOFO:
To what extent:
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/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Specific to this NOFO:
To what extent:
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?
To what extent:
Additional Review Criteria
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.
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 Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate 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
Not applicable
Renewals
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
Not applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
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) (i.e., 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 NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications 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 will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDSC) Council. The following will be considered in making funding decisions:
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that 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.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
If a recipient is successful and receives a Notice of Award, 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.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 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.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the Network and that NIH staff will be given the opportunity to offer input to this process. The Project Scientist(s) will participate as members of the Steering Committee and will have one vote. The Project Scientist(s) will have the following substantial involvement:
Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
Areas of Joint Responsibility include:
Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage, assess, and disseminate the Network model. The recipients and the Project Scientist(s) and PO will meet in person at least once per year with the program Steering Committee. Steering committee meetings may also occur virtually on a quarterly schedule or as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results. PDs/PIs, key co-investigators, and pre- and post-doctoral trainees, especially those who are members of underrepresented minority groups or those from different but related disciplines, are eligible to attend these meetings. The Project Scientists will have one collective vote and other NIH staff will serve as non-voting members. The Chair of the Steering Committee will be selected by the Steering Committee.
The Steering Committee will serve as the main scientific body of the program. The Steering Committee will be responsible for coordinating the activities being conducted by the program. The Steering Committee membership is defined in Part 2. Section 1. Funding Opportunity Description. The Steering Committee may add additional members, and other government staff may attend the Steering Committee meetings as desired. The Steering Committee may establish working groups as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The Network Steering Committee will have the overall responsibility of assessing and prioritizing the progress of the various working groups and other needed subcommittees.
The DCoE recipient agrees to work collaboratively to:
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.
3. Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the 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.
4. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
Awardees will provide updates at least annually on implementation of the PEDP
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. 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 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: 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: GrantsInfo@nih.gov (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: support@grants.gov
Argenia Doss
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-6369
Email: argenia.doss@nih.gov
Laura Mamounas
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5745
Email: mamounal@ninds.nih.gov
Sanoj Suneja, Ph.D.
National Institute on Aging (NIA)
Phone: 301-402-7710
Email: sunejas@mail.nih.gov
Jason Wan, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Phone: (301) 594-9898
Email: jasonwan@mail.nih.gov
Stacy E. Ferguson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3504
Email: fergusonst@niaid.nih.gov
Sangeeta Bhargava, PhD,
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: bhargavas@mail.nih.gov
Faye Chen, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5055
Email: chenf1@mail.nih.gov
Jyoti G. Dayal, M.S.
National Human Genome Research Institute
Telephone:(301) 480-2307
Email: jyotig@nhgri.nih.gov
Bracie Watson, Jr.
National Institute on Deafness and Other Communication Disorders (NIDCD)
Email: watsonb@nidcd.nih.gov
Melissa Parisi, MD, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6880
Email: parisima@mail.nih.gov
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email:nindsreview.nih.gov@mail.nih.gov
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@mail.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.