Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of 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)

Funding Opportunity Title
Diagnostic Centers of Excellence for the Undiagnosed Diseases Network (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project Cooperative Agreements

Announcement Type
New
Related Notices
  • October 16, 2023 - Notice of Availability of Frequently Asked Questions (FAQs) for PAR-23-289. See Notice NOT-NS-23-112.
  • August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Funding Opportunity (FON) Number
PAR-23-289
Companion Funding Opportunity
PAR-23-171 , X01 Resource Access Program
RFA-NS-22-051 , U2C Resource-Related Research Multi-Component Projects and Centers Cooperative Agreements
RFA-NS-23-004 , U01 Research Project (Cooperative Agreements)
Number of Applications

Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)
93.853, 93.867, 93.846, 93.865, 93.855, 93.121, 93.866, 93.172, 93.173
Funding Opportunity Purpose

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.

Key Dates

Posted Date
August 31, 2023
Open Date (Earliest Submission Date)
October 03, 2023
Letter of Intent Due Date(s)

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).

Expiration Date
November 04, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Conformance to all requirements (both in the 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.

Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

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:

  1. Continuing the proven success of the UDN in improving the clinical evaluation of difficult-to-diagnose patients using a collaborative team approach and investigating and validating promising new diagnostic technologies.
  2. Facilitating research into the etiology of undiagnosed diseases by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures.
  3. Promoting a broader integrated and collaborative community across multiple Clinical Sites and among laboratory and clinical investigators prepared to investigate the genetic, pathophysiologic, cell biologic, and molecular mechanisms underpinning these difficult-to-diagnose conditions.

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:

  1. Scale clinical capacity to engage more participants across the US by increasing diagnostic efficiencies and incorporating community and third-party payer support for patient services. To achieve this goal, DCoEs are expected to:
    • Provide a plan to enroll an achievable number of participants based on the site’s experience, outreach capabilities, community needs, and budget. Awarded DCoEs are expected to work with the DMCC to develop an enrollment plan that utilizes a tiered evaluation approach and is based on the specific diagnostic needs of each participant (e.g., Tier 1: initial screening/record review; Tier 2: telemedicine visits; Tier 3: comprehensive on-site clinical evaluations for a subset of participants; Tier 4: research activities) with plans to scale up enrollment as diagnostic efficiencies are established.
    • Work closely with the DMCC and other DCoEs to improve the efficiency and cost-effectiveness of the clinical evaluation (e.g., Artificial Intelligence (AI)/machine learning and other innovative tools for record review and data analysis, tiered evaluation strategies and remote visits as described above, etc.), while still providing a comprehensive and expeditious clinical evaluation of participants.
    • Although DCoEs are encouraged to enroll and evaluate participants with disorders in any clinical specialty, applicants have the option to specialize in one or more areas of clinical practice including but not limited to pediatrics, neurology, ophthalmology, cardiology, gastroenterology, immunology, metabolism, environmentally-linked or infectious diseases, etc.
    • Seek reimbursement when possible from non-NIH sources for patient services, for example, by billing insurance, utilizing support from their institutions, outside partnerships, foundations, or private donors.
    • Collaborate with the DMCC and other DCoEs to incorporate health economics approaches into network operations and establish additional outside funding partnerships including institutional and philanthropic support, and private donations to support the expansion and sustainability of the UDN in Phase III.
  2. Expand access to the UDN for individuals and groups who historically have not benefited from modern diagnostic investigations due to race, ethnicity, socioeconomic status, geographic location, sex/gender, linguistic or other systemic barriers. To achieve this goal, DCoEs are expected to:
    • Collaborate with the DMCC to recruit and enroll individuals from populations defined by the NIH to experience health disparities in the US.
    • Partner with community collaborators that serve populations defined by the NIH to experience health disparities, including but not limited to academic institutions, local healthcare systems and hospitals, state and local public health agencies, community-based organizations, faith-based organizations, and rural or urban community health centers including those that serve economically disadvantaged individuals. At least one of the partnerships must be a community healthcare organization that provides services for economically disadvantaged individuals who are under/uninsured. Applicants are expected to establish cooperative and mutually beneficial partnerships with the community collaborators beyond simply providing patient referrals to the DCoE (e.g., opportunities for the community collaborators to partner with the DCoE in the clinical evaluation, gain clinical and research expertise in undiagnosed diseases, engage fully in UDN activities, and participate in DCoE decisions that impact the partnership) and provide appropriate reimbursement for research performed by the community collaborator. Note: the partnerships with community collaborators may also comprise a component of the applicant’s Plan for Enhancing Diverse Perspectives (PEDP), as described below.
    • Prioritize NIH funds to cover the patient costs of under/uninsured participants along with research studies that facilitate a diagnosis.
  3. In addition to continuing the fruitful genomic approaches established in Phase I/II of the UDN, Phase III DCoEs are expected to propose and develop innovative strategies to investigate other potential causal factors in undiagnosed diseases such as environmental insults, infectious, oncologic, immunologic, or complex genetic disorders.
  4. Ensure that participants consistently receive a high-quality experience, for example, by collaborating with the DMCC to survey and incorporate input from patients, caregivers and family members into the practice of the UDN.

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)

  • This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as an attachment in Other Project Information (see Section IV). The partnerships with community collaborators (described above) may comprise a component of the PEDP.
  • Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

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:

  • The contact PD/PI of NIH-awarded DCoEs and the UDP PI
  • The contact PD/PI of the DMCC
  • A representative from the participating undiagnosed diseases patient advocacy group(s). The patient advocacy groups will have one collective vote
  • NIH Program Official(s)/Projects Scientist(s) from participating Institutes. NIH will have one collective vote
  • As the Network evolves, other key stakeholders may be invited to serve on the Steering Committee as appropriate (e.g., outside funding or resource partners, the contact PD/PI of UDN research cores)

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:

  • Applications that propose clinical trials or do not include a PEDP will be considered non-responsive and will not be reviewed.

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

Section II. Award Information

Funding Instrument

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.

Application Types Allowed
New
Renewal

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.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

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.

Award Project Period

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

All organizations administering an eligible parent award may apply for a supplement under this NOFO.

Higher Education Institutions

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

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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 Government

  • 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

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.

Required Registrations

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.

  • 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.

Eligible Individuals (Program Director/Principal Investigator)

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. 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.

Letter of Intent

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:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

Argenia Doss
Telephone: 301-827-6369
Email: argenia.doss@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

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:

  • The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate.
  • Where possible, applicant(s) should align their description with these required elements within the research strategy section.
  • The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. For example, the requirement to partner with community collaborators (described in Section I. Funding Opportunity Description) may comprise a component of the applicant's PEDP.
  • The PEDP should include a timeline and milestones for relevant components that will be considered as part of the review.

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

  • Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
  • Description of any planned partnerships that may enhance geographic and regional diversity.
  • Plan to enhance recruiting of women and individuals from groups historically underrepresented in the biomedical, behavioral, and clinical research workforce.
  • Proposed monitoring activities to identify and measure PEDP progress benchmarks.
  • Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early-and mid-career researchers.
  • Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers, and co-investigators from diverse backgrounds.
  • Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
  • Publication plan that enumerates planned manuscripts and proposed lead authorship.
  • Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.
  • For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative.nih.gov/about/plan-enhancing-diverse-perspectives-pedp
  • Applications must include a PEDP, including milestones, submitted as an attachment in Other Project Information.

Applications that do not include these attachments will be considered non-compliant and will not move forward in review.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

Address the following elements in the relevant Biographical Sketches (and as appropriate):

  • Knowledge and prior experiences of the PD(s)/PI(s) and key personnel in leading and managing projects involving the clinical practice and research of rare and undiagnosed diseases.
  • Clinical expertise in managing and diagnosing patients with difficult-to-diagnose conditions including expertise and knowledge of advanced diagnostic testing strategies, detailed clinical phenotyping, DNA and RNA sequencing, clinical genomics/metabolomics and other specialized clinical and laboratory testing used to diagnose challenging cases; include specialties/subspecialties of physicians if applicable.
  • Expertise in medical genetics including bioinformatics expertise to identify pathogenic variants from human DNA sequence data and other clinical genomics, metabolomics, immunologic and/or exposome investigations.
  • Provide examples where the PD(s)/PI(s) collaborate with teams of scientists to make difficult diagnoses and disseminate findings to network members and/or the broader undiagnosed/rare disease research community.
  • Experience and success in leading or coordinating diversity outreach activities to engage populations defined by the NIH to experience health disparities.
  • Expertise in health economics or implementation science approaches relevant to improving and sustaining the UDN model.

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.

R&R or Modular Budget

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.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

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:

  • Prior experiences and success of your site in: recruiting, enrolling, conducting the clinical evaluation, and diagnosing individuals with difficult-to-diagnose disorders, including those from populations defined by the NIH to experience health disparities. For applicants submitting a Renewal application (i.e., recipients of an award under RFA-NS-23-004), describe your site’s progress in evaluating and diagnosing UDN participants enrolled at your site including whether previous enrollment milestones were met; describe specific activities your site engaged in that contributed to the overall success of the UDN.
  • Unique strengths such as systems- or disease-specific clinical expertise available at your site including the specific area(s) of clinical practice that your site intends to pursue, and your willingness and approach for making such expertise available network-wide.
  • The proposed approaches, and potential alternatives, to performing the various DCoE tasks including plans for: participant recruitment, selection, consent, and counseling; clinical evaluation and data collection; investigation of family members, when appropriate; communicating the final diagnosis and, if feasible, recommendations for medical management and treatment of participant; return of information to affected participants, their families, and their referring physicians; transfer of care to referring clinicians; participant follow-up for psychosocial, health, and other relevant outcomes; data analysis and re-analysis when appropriate; data sharing and publication(s); and complementary laboratory and gene function studies, as appropriate to make a diagnosis.
  • Novel approaches that increase the efficiency, yield, and cost-effectiveness of the diagnosis (e.g., remote visits, tiered evaluation strategies, AI/machine learning and other innovative tools for record review and data analysis, etc.), while still providing a comprehensive and expeditious clinical evaluation of participants. Describe plans to collaborate with the DMCC and other DCoEs to scale clinical capacity of the UDN in Phase III by increasing diagnostic efficiencies.
  • In addition to advancing genomic approaches, describe innovative strategies to investigate non-genomic causal factors in undiagnosed diseases such as environmental insults, infectious, oncologic, or immunologic conditions, or approaches to diagnose complex genetic disorders.
  • Site-specific efforts and plans to collaborate with the DMCC to ensure that participants consistently receive a high-quality experience (e.g., by collaborating with the DMCC to survey and incorporate input from patients, caregivers and family members into the practice of the UDN).

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:

  • In Phase III, outreach and recruitment efforts will be a shared responsibility between the DMCC and the DCoE and will require close collaboration to achieve the goal of expanding UDN access to broader populations in the US including populations defined by the NIH to experience disparities. To increase diagnostic efficiencies, awarded DCoEs are expected to work with the DMCC to develop an enrollment plan that utilizes a tiered evaluation strategy and is based on the specific diagnostic needs of each participant; for example: Tier 1: cases where initial screening and record review are sufficient to make a diagnosis or recommendation to the participant and referring provider; Tier 2: cases that require telemedicine visits to collect additional information for the diagnosis; Tier 3: a subset of difficult cases not diagnosed through the Tier 1 or 2 evaluations that may require advanced diagnostic tools and approaches, including a comprehensive on-site clinical evaluation (e.g., as described in the Phase II UDN Manual of Operations); Tier 4: a smaller subset of cases that require gene function studies in model organisms/systems or other research investigations to facilitate a diagnosis. Provide a plan to enroll and evaluate an achievable number of participants, including annual enrollment numbers for each tier, based on your site’s experience, outreach capabilities, community needs, and budget. Historically, Phase I/II Clinical Sites evaluated an average of 20-30 participants per year depending on specific budgets and approaches (see UDN Facts and Figures); it is important to note, however, that Phase III goals include amplifying enrollment projections. Describe your site’s plans for evaluating participants using a tiered approach including plans to scale up enrollment as diagnostic efficiencies are established.
  • Describe the DCoE’s outreach plans and plans to collaborate with the DMCC and other Network members to recruit and enroll participants specifically from populations defined by the NIH to experience health disparities, including those from racial and ethnic minority populations, from urban and rural areas who are economically disadvantaged and medically underserved and/or those with limited English proficiency.
  • Applicants are required to partner with one or more community collaborators as described in Section I. Funding Opportunity Description, which can also comprise a component of the PEDP. At least one of the partnerships must be a community healthcare organization that provides services for economically disadvantaged individuals who are under/uninsured. In this section, provide an overview of the role of the community collaborator(s) in partnering with the DCoE to expand access to expert diagnostic services for populations defined by the NIH to experience health disparities, and the specific activities to be performed by the collaborator (e.g., outreach activities to historically underserved populations in their local catchment areas, enrollment of participants at their site, partnership with the DCoE in the clinical evaluation of participants, telemedicine visits to ease the burden on participants, etc.). Describe any unique strengths and perspectives of the community investigator(s) and their affiliation(s) to engage historically underserved populations who could benefit from the UDN (include a Biosketch for all community key personnel). Applicants must describe plans to establish cooperative and mutually beneficial partnerships with the community collaborators that go beyond simply referring patients to the DCoE (e.g., opportunities for the community collaborator to partner with the DCoE in the clinical evaluation, gain clinical and research expertise in undiagnosed diseases, engage fully in UDN activities, and participate in DCoE decisions that impact the partnership) and provide appropriate reimbursement for research performed by the community collaborator.
  • The costs for clinical services of economically disadvantaged UDN participants who are under/uninsured must be prioritized and described in application (in Attachment 1, Other Project Information). In the Budget pages and justification, include plans to support the travel and room and board for economically disadvantaged UDN participants, either through outside partnerships or using NIH funds.

Integration and collaboration are essential tasks for DCoEs and other UDN members. Applicants are required to describe the following:

  • In Phase III, the Network plans to promote greater collaboration across sites to help solve challenging and difficult cases that could benefit from broader discussion, consultation, and possibly scientific collaboration between DCoEs. State your site’s willingness to engage in Network-wide discussions and collaborations to help solve particularly difficult cases, and strategies for accomplishing this goal.
  • Plans to collaborate with the DMCC, other DCoEs, Network research cores and laboratories, and NIH Program Officials and Project Scientists to design and implement Network protocols, a Manual of Operations, and participate in Steering Committee, case review, diagnostic consultation, and working group meetings as established by the Steering Committee.
  • Plans to collaborate in identifying and solving operational problems involving participant outreach, recruitment, communication with applicants and participants, improving participant experiences, data collection, quality assurance and refinement of protocols to improve network efficiencies.
  • Plans to collect data on genotype/genomics, phenotype, metabolomics, and environmental exposures, including plans to work with the DMCC to optimize data collection (such as use of standard collection tools or ontologies) and analysis strategies, and facilitate public access to the Network data through the DMCC and submission to public data repositories such as AnVIL.
  • The willingness of applicants to adhere to network-wide policies and procedures for the key DCoE functions described above as well as network-defined processes and timelines for recruitment, data collection, and accurate submission of all required tracking and participant data to the DMCC. Describe plans for, and willingness to abide by Memoranda of Understanding (MOU) and other sharing and data use agreements potentially needed for data and sample sharing within the Network, NIH, research community, and public, as determined by the Steering Committee and data sharing strategy.
  • Applicants should indicate their willingness to participate in a network that uses a single IRB. The UDN will use a single IRB at the intramural NIH to accelerate IRB approval of network-wide protocols.

Bioinformatics Plan

Propose a plan for bioinformatics analysis to include:

  • Plans for how bioinformatics infrastructure, capabilities, and computational resources in place (or readily obtainable) as described in Facilities and Other Resources will be leveraged.
  • Bioinformatics approaches and innovation to provide the best utilization of the data produced by the Network including innovative approaches capable of identifying rare and novel diagnoses.
  • Plans to collaborate with the DMCC and other Network DCoEs to develop and disseminate bioinformatics tools and resources within the Network and to the scientific community to improve the UDN model.

Assessment, Dissemination, and Outreach

Propose a plan for assessment, dissemination, outreach, and training to include:

  • Assisting the DMCC with developing and implementing appropriate educational and outreach materials for participants, clinicians, and other researchers.
  • Collaborating with the DMCC and other DCoEs to assess and disseminate data, protocols, consent materials, and methods relevant to undiagnosed diseases and derived both within and outside the Network.
  • Conducting training activities to expose students, fellows, staff, faculty, and community collaborators to the Network model and utilization of Network data and tools.

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.

  • Methods, protocols, tools, and software should be well-documented and where applicable made available via version-controlled public repositories.
  • Solutions that enhance reproducibility when used by the community and ability of the community to integrate into automated pipelines should be emphasized.
  • In the Resource Sharing Plan, a plan for sharing software should describe how improvements or tool customizations will be managed and disseminated to the scientific community. Applicants should take responsibility for creating the original and subsequent official versions of a piece of software.
  • Model organisms and cell lines should be made available through public repositories.

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:

  • 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 (DMS) Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
  • Data sharing under this NOFO is required to increase the value of the significant public investment in the creation and operation of the Network. Consistent with achieving the goals of the program, NIH expects that participant datasets from the Network will be widely shared in a timely manner with the scientific community for research, while carefully observing standards of patient privacy, confidentiality, and management of health information. Relevant data, including that which is associated with publications, must be made available to the broader community upon publication or at the end of the period of performance as required by the DMS Policy.
  • In accordance with the FAIR Principles, the DMS Plan should be consistent with Network policies for obtaining informed consent for broad data sharing, using standardized data collection protocols and survey instruments for capturing data, as appropriate; and using standardized notation for metadata (e.g., controlled vocabularies or ontologies) to enable the harmonization of datasets for secondary research analyses. See examples of Network policies for Phase II in Phase II UDN Manual of Operations.
  • Use of Common Data Elements in NIH-funded Research: Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g., genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (https://cde.nlm.nih.gov/home) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.
  • Sites must work with the DMCC to register de-identified sequence data, associated metadata, and phenotypic data derived from Network participants in a timely manner with dbGaP and deposit data into AnVIL. Timelines for submissions will be defined by the Network but are expected to be on a rolling and frequent basis such as monthly.
Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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.

PHS Assignment Request Form

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

4. Submission Dates and Times

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.

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.

7. Other Submission Requirements and Information

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.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

For 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:

  • The overall goals and objectives of the UDN and assist in the diagnosis of participants who suffer from rare or difficult-to-diagnose diseases?
  • Enhancing our understanding of previously undiagnosed diseases?
  • The Phase III goal of expanding UDN access to individuals from populations defined by the NIH to experience health disparities, including establishing meaningful partnerships with community collaborator(s) to achieve this goal?
  • The goal of scaling clinical capacity to engage more participants across the US, for example, by increasing diagnostic efficiencies and incorporating community, institutional and third-party payer support for patient services when allowable?
  • To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives (PEDP) further the significance of the project?

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:

  • The required experience and expertise, including bioinformatics expertise, to evaluate and diagnose individuals with rare and/or difficult-to-diagnose conditions and are they recognized in the field as expert diagnosticians?
  • A track record of meeting enrollment milestones?
  • A track record of working collaboratively and disseminating findings?
  • A track record of collecting, analyzing, and publishing phenotypic, genomic and exposome data?
  • The appropriate experience in managing complex, projects involving teams of scientists?
  • The skills and experience needed to coordinate outreach activities and engagement of individuals from populations defined by the NIH to experience health disparities?
  • Do the efforts described in the PEDP strengthen and enhance the diverse expertise and perspectives required for the project?

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?

Specific to this NOFO:

To what extent:

  • Have the applicants proposed creative new strategies that have the potential to increase the efficiency, yield, and cost-effectiveness of the diagnosis (e.g., remote visits, tiered evaluation strategies, AI/machine learning and other innovative tools for record review and data analysis)?
  • Are the bioinformatics approaches described state-of-the-art and likely to provide the best utilization of the data produced for the Network?
  • Does the proposal include creative approaches to engage and recruit individuals from populations defined by the NIH to experience health disparities? Do the partnerships with the community collaborator(s) contribute to the innovation of the project?
  • Will this project advance not only the development of innovative genomics technologies but also strategies to investigate other potential causal factors in undiagnosed diseases such as environmental insults, infectious, oncologic, immunologic, or complex genetic disorders?
  • Will the efforts described in the PEDP meaningfully contribute to innovation?
  • As new technologies become available, how well is the research team poised to recognize when they are sufficiently developed and validated to be added to the Network protocols?

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:

  • Does the applicant propose an effective plan to enroll and evaluate undiagnosed participants with plans to scale up as diagnostic efficiencies are established (e.g., by proposing a tiered evaluation approach, telemedicine visits, etc.)? Are the annual enrollment numbers sufficient to achieve the goals of the NOFO and commensurate with the budget?
  • Are the conceptual design and overall strategy likely to improve the efficiency, yield and cost-effectiveness of the diagnosis and contribute to our understanding of these previously undiagnosed conditions?
  • Does the applicant have an effective outreach and recruitment plan including engaging and enrolling individuals from populations defined by the NIH to experience health disparities?
  • Are the plans to partner with the community collaborator(s) meaningful, mutually beneficial, and likely to expand UDN access to minority health and other populations defined by the NIH to experience health disparities?
  • Does the project, including the bioinformatics plan, propose cutting edge, innovative approaches capable of diagnosing rare and novel conditions?
  • In addition to advancing genomics approaches, does the applicant propose effective strategies to investigate other causal factors in undiagnosed diseases such as environmental insults, infectious, oncologic, immunologic, or complex genetic disorders?
  • Are plans in place to collaborate with the DMCC to ensure that participants receive a high-quality experience?
  • Does the applicant seek reimbursement, when possible, from non-NIH sources for patient services and routine testing (e.g., billing insurance, utilizing support from their institutions, outside partnerships, foundations, etc.)? In addition to research, are NIH resources being appropriately used to support the clinical services and travel expenses of economically disadvantaged and/or under/uninsured participants?
  • Are the PEDP plans well-developed and feasible and likely to contribute to the overall success of the project?

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?

  • Specific to this NOFO:

To what extent:

  • Will participants receive a high-quality experience at the site?
  • Are the resources, equipment, and infrastructure available and in place (or readily obtainable) to support the clinical evaluation of participants at the DCoE?
  • Are the bioinformatics infrastructure and capabilities and computational resources in place (or readily obtainable) and adequate to support the project?
  • Are institutional resources and infrastructure being committed or leveraged?
  • Are adequate plans in place for the evaluation and referral for care of under/uninsured participants including those from populations defined by the NIH to experience health disparities?
  • Will features of the environment described in the PEDP (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?

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

Additional Review Considerations

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:

  • 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.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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.

Cooperative Agreement Terms and Conditions of Award

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:

  • Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
  • Determining research approaches, designing protocols, setting project milestones, and conducting research.
  • Participating in group activities, including a network-wide Steering Committee and working groups as needed.
  • Refining and implementing the resulting consensus framework at their DCoE and network-wide, in collaboration with the Data Management Coordinating Center (DMCC) and NIH UDP.
  • Providing protocols, reports, and data in a timely fashion as agreed upon by the Steering Committee.
  • Submitting all data from Network participants as soon as they are collected to the DMCC for quality control and compilation in a network-wide dataset to be made available to all Clinical Sites (including the NIH UDP), as agreed upon by the Network Steering Committee, and deposited in database repositories such as AnVIL .
  • Preparing abstracts, presentations, and publications and collaborating network-wide in making the public and professionals aware of the program.
  • Assessing and disseminating data, protocols, consent materials, and methods developed for or derived from within and outside the Network.
  • Developing and implementing appropriate educational materials for participants, clinicians, and other researchers.
  • Adhering to policies regarding data access, publication, and intellectual property established by the NIH and the Network Steering Committee.
  • Abiding by common definitions, protocols, and procedures, as chosen by a majority vote of the Network Steering Committee.
  • Accepting and complying with study policies established by NIH and with additional non-conflicting policies approved by the Network Steering Committee.
  • Submitting periodic progress reports in a standard format, as agreed upon by the Steering Committee and Trans-NIH Network Working Group.
  • Attending and participating in the Network Steering Committee meetings and accepting and implementing decisions by the Trans-NIH Network Working Group, as appropriate. The PI(s)/PD(s) must plan at least one in-person meeting per year with the External Advisory Committee, Steering Committee, and other DCoE PIs/PDs.

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:

  • Participating with the other Network Steering Committee members in addressing issues that arise with Network planning, operation, assessment, and data analysis. The Project Scientist(s) will assist and facilitate the group process and not direct it.
  • Serving as a liaison, helping to coordinate activities, including acting as a liaison to other NIH Institutes/Centers, and as an information resource for the recipients. The Project Scientist(s) will also help coordinate the efforts of the Network with other groups conducting similar efforts.
  • Attending all Steering Committee meetings as a voting member and all Working Group meetings, assisting in developing operating guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist(s) will be responsible for working with the grantee as needed to manage the logistic aspects of the Network.
  • Reporting periodically on Network progress to the Trans-NIH Network Working Group and through it to the NIH National Advisory Neurological Disorders and Stroke Council.
  • Serving on subcommittees of the Steering Committee and Working Groups as appropriate.
  • Assisting recipients in the development, if needed, of policies for dealing with situations that require coordinated action.
  • Providing advice on the management and technical performance of the award.
  • Assisting in promoting the availability of the data and related resources developed in the course of this program to the scientific community at large.
  • Participating in data analyses and interpretations where warranted.
  • Other Trans-NIH Network Working Group staff may assist the recipient as designated by the Program Official.

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:

  • Assist in refining a common approach for participants with undiagnosed diseases.
  • Participate in network-wide processes for participant selection and assignment to specific DCoE for evaluation.
  • Provide secure, accurate, and timely data submission.
  • Participate in presenting and publishing new processes and substantive findings.
  • Assess and disseminate the Network model.
  • Participate in the governance of the Network as a member of the Steering Committee.
  • Interact with other relevant NINDS and participating NIH Institute activities, as needed, to promote synergy and consistency among similar projects.
  • Partner with community collaborators to challenge and seek to advance or change current research or clinical practice paradigms used to care for populations defined by the NIH to experience health disparities, for example, by using novel theoretical concepts, approaches or methodologies, instrumentation, or interventions.

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.

Section VII. Agency Contacts

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

Application Submission Contacts

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: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

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

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email:nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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.

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