Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No Late Applications will be accepted for this Funding Opportunity Announcement.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) 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.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background:

Neuropathological assessment of postmortem brain tissue in many Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) consist of multiple pathologies resulting in mixed diagnoses. Understanding cross-AD/ADRD pathologies often requires collaboration of multiple brain banks and the sharing/re-staining of tissue or slide sets, especially for less common pathology types. Recent advances in digital neuropathological slide imaging have simplified slide-sharing processes and enabled the use of machine-learning (ML) and artificial intelligence (AI) analytic approaches. (For the purposes of this FOA, AI/ML is inclusive of machine learning (ML), deep learning (DL), and neural networks (NN).) However, making data AI/ML-ready is not simply formulaic. Aspects of data, such as the representation of information, presence of noise, specificity or uncertainty of labels / nomenclature, data provenance, digitization parameters, brain collection and preservation information, filtering, stain, or antibody used, spurious artifacts, imaging scanner and resolution, can influence the computational feasibility of AI/ML learning and the accuracy of the resulting models in ways that are currently difficult to predict without testing. Therefore, to most effectively use AI/ML in digital neuropathology, metadata data standards that are machine-readable must be developed. Further, discovering and identifying imbalances in the data, such as sampling biases, or other attributes of the dataset that may affect researchers’ interpretations of results when using the data for AI/ML and improve the ethical reuse of data.

Developing advanced approaches to digitally share neuropathological slides will enable the discovery of complex interactions in pathology across cases and disease areas. To date, there is a lack of standardization and an inherent interoperability among various neuropathology slide technologies and scanners that hinders broad data sharing and cross lab/bank analyses. Many of the most common whole slide scanner brands have proprietary image formats and metadata standards creating an obstacle to slide sharing across sites and banks. Development of a metadata image standard, a common image format/standard and/or tools capable of reading all slide scanner image formats would lower this obstacle to data sharing. Additional barriers to broad sharing and analysis are the extensive data storage requirements created by each case, series, and brain bank. To address this issue, other fields have incorporated a system of federating data repositories such that distributed repositories across multiple sites are integrated virtually and data at each site is incorporated into one virtual federated repository with a single point of access. Though the federated approach reduces the need for a single large data storage site and eliminates the burden of uploading large digital datasets to that single site, it presents multiple other IT challenges involving access, security, and analytics. Examples of similar efforts can be found in other scientific areas. For example, the NIH, through several lines of effort (e.g. NIH Big Data to Knowledge (BD2K) and BRAIN Initiative) have assisted in the development of data standards (e.g. NIFTI), standardized data structures (e.g. BIDS; https://bids.neuroimaging.io/index.html), and metadata that best enable open science practices along with developing software platforms (e.g. ENIGMA; https://commonfund.nih.gov/bd2k/centers ) for multisite human neuroimaging and genetic analyses across data repositories and accommodating differences in global data sharing policies.

In 2019, NINDS convened a workshop with experts in Chronic Traumatic Encephalopathy (CTE), AD and other ADRDs, and Traumatic Brain Injury (TBI) to outline the challenges and opportunities for advancing the neuropathology and neuropathological diagnoses for CTE (site website: https://www.ninds.nih.gov/news-events/events/neuropathological-diagnosis-chronic-traumatic-encephalopathy-cte-next-steps-workshop). Workshop attendees agreed that, due to mixed pathology, larger samples from populations with multiple injury mechanisms is needed to further distinguish CTE from other neurodegenerative process. Further, attendees suggested that improvement in the infrastructure related to data sharing, particularly around more advanced analytic methods, were needed to rigorously compare cases with and without TBI across a spectrum of brain banks that specialized in various neurodegenerative diseases along with unaffected controls. To partially address the need for developing data standards for TBI- related human neuropathological studies, NINDS convened multiple working groups and developed a set of Common Data Elements to standardized reporting of Neuropathological assessments in TBI (see: https://fitbir.nih.gov/chronic-tbi-related-neurodegeneration-cdes). This current FOA was developed to further advance human neuropathological data infrastructure, outlined in the 2019 workshop, by developing a resource for creating digital imaging data standards, metadata standards, and IT solutions for digital library federation in an effort to ease the burden of sharing digital slides, encourage collaboration, and enable advanced analytic methods such as machine learning and artificial intelligence methods across multiple brain banks.

This FOA is in alignment with the National Plan to Address Alzheimer’s Disease to prevent and effectively treat AD/ADRDs by 2025. ADRD are defined as Frontotemporal dementia (FTD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), Lewy body dementias (LBD) and Multiple Etiology Dementias (MED). Starting in 2012, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) have held research summits to assess the needs and set AD/ADRD research implementation milestones. The NINDS ADRD Summit in 2022 resulted in the current ADRD research priorities, which this initiative is responsive to, and aims to advance the state-of-the-science toward meeting Goal 1 of the National Plan.

Specific Research Objectives:

The purpose of this funding opportunity is to create a resource in the form of an open-source software platform (referred to below as Open-source Federation Platform) that creates a single access portal that includes the tools, processes, and standards for enabling and enhancing data sharing and analysis of human digital neuropathological slides across multiple geographically distinct brain banks. The file formats, nomenclature, data standards and metadata standards developed are expected to enhance digital neuropathology data’s ML/AI-readiness by including critical elements by making the data machine-readable. Efforts toward developing standards are expected to consider current standards such as the NINDS-supported FITBIR Neuropathology Common Data Elements (CDEs; https://fitbir.nih.gov/chronic-tbi-related-neurodegeneration-cdes). Applicants must work collaboratively with other awardees under this FOA to create common image-level metadata standards for digital pathological images, a common study-level metadata format to describe the overall specimen characteristics and tissue processing (preferentially the existing NINDS Neuropathology CDEs would inform this metadata standard) to enable the images to be accessible in a machine-readable format. Development of the Open-source Federation Platform must have a single access portal that enables access to digital slides across at least three geographically-distinct digital neuropathology brain banks. This federation platform must include a common searchable catalog, data curation, and solutions (either integrated into the platform or via Application Programming Interfaces (API)) for cross-site image annotation and analyses. The Open-source federation platform must be capable of accessing and allow analysis of images obtained from multiple commonly used digital slide scanners; including but not limited to Aperio/Leica, Olympus, Zeiss, Phillips, and Perkin Elmer. A critical feature of this FOA is developing the platform and associated tools and standards to support the broad sharing of neuropathological data to further advance research in this area, including the development of a digital resource for distribution and sharing of assessed neuropathological tissue.

Examples of future uses of this Open-source Federation Platform include, but are not limited to:

• Cross-site validation of neuropathological findings in a specific AD/ADRD relevant disease area.
• Replication of results using digital slides from multiple digital libraries.
• Enhancing inclusion of tissue and slides from minority health and NIH-designated populations that experience health disparities (see: Minority Health and Health Disparities: Definitions and Parameters (nih.gov)
• Assessing the characteristics of mixed-pathology across multiple AD/ADRD disease areas from multiple digital slide libraries.
• Calculating specificity and selectivity of a specific neuropathological feature across multiple AD/ADRD disease areas and multiple digital slide libraries.
• Addressing issues of sample selection bias by including cases across multiple sites.
• Addressing statistical issues around sample size, power, and generalizability.
• Advanced Analytics, including Machine Learning, approaches across multiple AD/ADRD disease areas for unsupervised classification of cases based on neuropathological features using data from multiple digital slide libraries.
• Enhanced access to cases from multiple digital slide libraries for Neuropathological Diagnostic Consensus Conferences.
• Access to rare or unusual cases for training and/or analyses.

Application Requirements:

Study design: Applications should include 2 primary objectives:

Objective 1) Development of data, metadata standards, and software processes:

• Develop image data standards, improve consistency in nomenclature, image annotation standards, cataloging, and slice and sample wide metadata.
• Develop software solutions and an Open-source federation platform/portal, coupled with administrative best practices for developing data use agreements, data quality and security. In this case, federate refers to the distribution of repositories across multiple sites being integrated virtually and data at each site is incorporated into one virtual repository with a single point of access.
• Perform frequent software testing and validation for the Open-source platform and other software solutions developed.

Objective 2) Proof of Concept study: Demonstrate the feasibility and utility of a Open-source Federation platform, the metadata and image standards and IT solutions by performing at least one proof of concept neuropathological comparison/study using digital human neuropathological slides from a federated repository of at least three geographically distinct digital slide libraries with slides scanned on at least two different slide scanners. The libraries used in any proof-of-concept study must include an extensive collection of AD and/or ADRD diagnosed tissue. NINDS also has an interest in tissue from persons with a history of TBI. Tissue should be accompanied by demographic, clinical and other phenotypic data

Milestones:

A project timeline including milestones is a required component of the application. Milestones are quantitative goals that can be used for go/no-go decision making as the project advances, and therefore should have quantitative criteria associated with them. Milestones will provide clear indicators of a project's continued success or emergent difficulties. Progress toward achievement of milestones will be evaluated by NIH Program Staff, and funding for the project may be discontinued if milestones are not met.

The NIH Program Official will contact the applicant to discuss the proposed milestones before the award. The Program Official will discuss with the Program Director(s)/Principal Investigator(s) any recommended changes to the research plan or suggestions from peer reviewers, and the plan will be revised as appropriate before the award.

Investigator team: The study team should specialize in collecting and evaluating tissue related to the spectrum of disease from normal aging and including different AD/ADRDs so that neuropathological comparisons can be made across a range of disorders. It is expected that a multidisciplinary team with expertise in digital image processing, data science, software engineering and neuropathological diagnosis of neurodegenerative disease will be needed. This multi-disciplinary team-science strategy should encourage cross-fertilization of knowledge and utilize appropriate subject matter expertise for interrogating data. Further, NINDS encourages applications from diverse teams of investigators, including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce. (See: NOT-OD-20-031: Notice of NIH's Interest in Diversity ).

This opportunity is specifically targeted at resource/tool/software development. Acquiring new tissue is not in scope. However, processing existing tissue (e.g., blocking, slicing, mounting, staining), restaining or reimaging existing tissue/slides for purposes related to the development and testing of the capabilities of the Open-Source Federation Platform can be conducted but justification for how the neuropathological tissue processing is will inform platform development or testing must be provided.

Non-responsive studies include:

• Applications that are not primarily focused on AD/ADRD.
• Applications/resources with no neuropathological expertise in human subjects or that propose to include non-human digital pathology
• Studies that propose collecting new tissue
• Applications that do not intend to broadly share software/tools and data by the end of the award period.
• Applications that do not include milestones

Non-responsive applications may be administratively withdrawn prior to peer review.

Data Sharing

To advance the goal of strengthening FAIR (Findable, Accessible, Interoperable, and Re-usable) and TRUST principles in data sharing, investigators will be expected to share code/scripts, analytic tools/statistical models, protocols/processes and metadata -- used or developed for harmonization, curation, and analysis -- through open-access repositories. Therefore, investigators are strongly encouraged to use open-source software, analytic tools, and programming languages to promote interoperability as well as reproducibility. In this way, the FAIR principles for data sharing and the rigor and reproducibility of research will be enhanced. Applicants who plan to utilize data not currently in their possession (originated from another party) must confirm availability of the data and demonstrate (at a minimum via a letter of support) the willingness and permissibility of the original investigators to share the data for the purposes of the harmonization, curation, secondary analyses, in accordance with all applicable rules for the protection of human subjects.

To ensure the maximal value of the project, applicants to this FOA are expected to include open-source cataloging of the processes and tools used for data image standards reading/conversion, cataloging, and creating a federate digital image repository. The digital library must be scalable and capable of data expansion and growth.

Diversity and health disparities:

All applicants proposing human subjects research are encouraged to focus on the recruitment and inclusion of individuals from racial and ethnic minority health and NIH-designated populations that experience health disparities and plans for doing so should be included in the application (see: https://grants.nih.gov/policy/inclusion.htm) and Minority Health and Health Disparities: Definitions and Parameters (nih.gov)).For all types of research proposals, NINDS encourages applications from diverse teams of investigators, including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce. Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds (see: NOT-OD-20-031: Notice of NIH's Interest in Diversity).

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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

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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant 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 full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

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

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 FOA. 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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement 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:

Nsini Umoh, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1447
Email: nsini.umoh@nih.gov

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

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

R&R Budget

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy

Specific aims: Provide the overall goals of the entire project and list separate Specific Aims to be accomplished, briefly outline the methods proposed, and summarize the expected outcomes.

Describe the research strategy to accomplish the specific aims, how the software and tools developed will be tested and validated, and how the study will advance research in this area, including the development of a digital resource for the distribution and sharing of assessed neuropathological tissue. Applications should include 2 primary objectives:

Objective 1) Development:

• Applicant must provide a plan for collaboration with other research teams and the neuropathology research community to develop metadata standards for digital images of neuropathology slides.
• Applicant must provide a plan for collaboration with other research teams and the neuropathology research community to develop metadata standards for study-level data related to the case, e.g. donors demographics, existing neuropathological diagnosis, tissue collection and processing details. It is expected that the existing NINDS Neuropathology CDEs will inform this study-level metadata standard.
• Proposal must develop an Open-source Federation Platform that creates a single access portal that includes the tools, processes, and standards for enabling and enhancing data sharing and analysis of human digital neuropathological slides across multiple geographically distinct brain banks. NINDS. The Platform much include single-point access to digital neuropathology slides from at least 3 existing, geographically-distinct neuropathology digital libraries. The digital libraries included as federated sites must have collections relevant to AD/ADRD disease areas. Description of the Platform should provide a description of the scalability (how many digital neuropathology libraries could ultimately be included) of the Platform.
• Proposals must describe how the images will be “machine readable” for enabling advanced analytic methods.
• Proposals must develop either a common image file format or demonstrate a software tool that allows reading and editing of existing proprietary image formats that have been created by the Neuropathology Digital Slide Scanner providers. The solution must be able to read and edit/annotate images from manufactures including but limited to Aperio/Leica, Olympus, Zeiss, Phillips, and Perkin Elmer.
• Applicants are expected to include community standards for neuropathological nomenclature related to anatomical areas, disease diagnosis, and pathological features.
• The Open-source Federation Platform must include the development of Application Programming Interfaces (APIs) that enables software used for analytics (e.g. R, python, and/ or other open source analytic tools), viewing, and annotation to communicate with and work within the Open-source Federation Platform environment.
• Proposals must include administrative best practices, preferably in the form of a Standard operating procedures manual, for developing data use agreements, data quality and federation-wide IT security.
• Proposals must provide a detailed description of regular software testing and validation to demonstrate progress toward the stated software solution goals.

Objective 2) Proof of Concept:

Proposals must include at least one, and preferably multiple proof-of-concept tests that demonstrate the utility and function of the Platform and associated tools. Proof-of-concepts tests must involve digital neuropathological images from AD/ADRD relevant cases and should demonstrate the robustness of the functionality related to catalog searching that allows for case selection on multiple factors (See: https://grants.nih.gov/policy/inclusion.htm). Proof-of-concept tests will also provide a demonstration of the image viewing and annotation capabilities with a focus on combining slide images obtained from different digital scanner systems. The tests chosen must challenge the systems capabilities and also demonstrate the platforms ability to enable advanced analytic methods such as machine learning approaches.

Additional imaging analyses of the existing federated repositories can be conducted as appropriate to test the tools/software development of this FOA.

Timeline and Proposed Milestones (required)

• Milestones must be provided under a separate, specific heading at the end of the Research Strategy Section and will be evaluated as part of the scientific and technical merit of the application.
• Quantitative milestones are required to provide clear indicators of a project's feasibility, continued progress or emergent difficulties and will be used to evaluate the application
• Please see “Project Milestones” (End of Section I) for guidance in writing Go-No Go, quantitative milestones.
• Provide a detailed timeline for the anticipated attainment of milestones and the overall goal. Indicate when it is anticipated that essential components of the project will be completed.
• Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.

Team Management Plan:

• Applicants are strongly encouraged to form multidisciplinary teams with expertise in AI/ML (e.g., MPI or Co-I with AI/ML expertise), data science, and neuropathological diagnosis of neurodegenerative disease. Describe the team's ability to design the details of the plans and to execute the research strategy.
• Describe how the team will work together (e.g., reporting of data and integrated review across teams with various disciplines, decision-making, etc.) over the course of the project (and include letters of support below). This description should include an outline of roles and responsibilities for each team member.

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:

Software and tools developed under this initiative are expected to be shared using Open Science principles, to guarantee the right of others to read, redistribute, modify, and freely use any software. The federated digital library is also expected to follow FAIR data sharing principles (https://www.go-fair.org/fair-principles/).

See NIH guidance on writing a data management and sharing plan: (https://sharing.nih.gov/data-management-and-sharing-policy/planning-and-budgeting-DMS/writing-a-data-management-and-sharing-plan)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof 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 FOA 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions 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.

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 proposed Studyaddress the needs of the research community that it will serve? Is the scope of activities proposed for the study appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research community?

Specific to this FOA:

• To what extent will the proposed study/specific aims advance research in this area? Including the development of a digital resource for distribution and sharing of assessed neuropathological tissue.

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the study? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing biomedical research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structureappropriate for the studyCenter? Does the applicant have experience overseeing the selection and management of subawards, if needed?

Specific to this FOA:

• Is each investigator on the team an established leader with a history of innovative work in their area of research?
• Is there appropriate neuropathological, AI/ML, and data science expertise to accomplish the aims?

Innovation

Does the application propose novel management strategies in coordinating the researchresearch projects the study will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of instrumentation proposed?

Specific to this FOA:

• To what extent does the application include leading-edge and innovative attributes in open-source cataloging of the processes and tools used for data image standards reading/conversion, cataloging, and creating a federated digital image repository?
• Will the proposed Open-source Federation Platform provide a resource that will enable future collaborative neuropathological approaches to address AD/ADRD-relevant neuropathological hypotheses?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research projects the study will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the projects, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the resource is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of theprojects? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of 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 FOA:

• Does the proposed approach allow for machine-readable solutions?
• Does the application include a detailed description of how to collaborate with other funded projects on metadata development for both image metadata and study-level metadata standards?
• Will the proposed plan for outreach to the broader neuropathology community provide sufficient opportunity for the broader neuropathology community to provide impactful input regarding the metadata standards?
• Does the Open-source Federation Platform have a single access point that has a searchable catalog containing at least 3 geographically distinct digital libraries?
• Does the Open-source Federation Platform allow a single-point access to view, annotate, and perform analysis on digital slides at all federated sites without having to download the images locally?
• Is the solution (either software reader or common file format or both) for reading images from multiple vendors available? Does this solution allow seamless combinatory use of digital images from multiple digital image scanner vendors?
• Is the proposed use of neuropathological nomenclature, within the platform, consistent with the neuropathology communities nomenclature standards; particularly those within the AD/ADRD research areas?
• Has the proposed Open-source Federation Platform included the appropriate APIs to enable slide viewing, annotation, and advanced analytic methods? Will the APIs included provide researchers using various software analytic tools access to the federated images?
• Is the software solution scalable?
• Does the study team have appropriate data use agreements?
• Is there a description or Standard Operating procedure manual for informing users about the best practices for developing data use agreements, material transfer agreements, assessing data quality, and IT security?
• Will the software be publicly available?
• Are digital slides on a safe/secure site or platform?
• Is there a detailed description for the timing and processes involved in software testing and validation? Are those testing procedures sufficiently rigorous to ensure that the software being developed is robust?
• Does the proposal provide at least one Proof-of-Concept test that includes integrating data from all federated sites and includes data scanned on scanners from multiple vendors?
• Does the proof-of-concept test demonstrate the ability to perform advanced analytics (e.g., machine learning) on images from multiple sites in a federated manner (i.e., not having to download images from each site to a single location)?
• If the proof-of-concept test includes additional tissue processing and slide scanning, is it justified for testing the software of platform?
• Does the proof-of-concept test assess all of the functionalities proposed to be available in the Open-Source Federation Platform? Including but not limited to digital slide annotation, catalog searching, case selection, analysis (either within the Platform itself or through an Application Programming Interface (API))
• Does the proof-of-concept test include AD/ADRD relevant cases?
• Are clear and quantifiable annual milestones creating go/no-go decision points for measuring the success of all the project's specific aims proposed?
• Does the project involve a collaboration with the AI/ML community (e.g., MPI or Co-I with AI/ML expertise)?
• Is there a strong plan for facilitating the teamwork/collaborative interactions (e.g., reporting of data and integrated review across teams with various disciplines, decision-making, etc.) for the project, including an outline of roles and responsibilities for each team member?
• Does the project include a plan for timely software testing to validate and verify the software and tools developed? Does applicant propose using the software/tool to perform multisite neuropathological analyses using a federated approach?

Environment

Will the institutional environment in which the studywill operate contribute to the probability of success in facilitating the research [program/projects/network/consortium] it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the study proposed? Will the study benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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 Animal 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

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Does the applicant propose a broad sharing plan of neuropathological data with the scientific community?

Reviewers will comment on whether the Resource/Data Sharing Plans 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 (generally the top half of applications under review) 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 FOA.

Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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 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.5. 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 FOA 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:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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 must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please 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 FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 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 (grant) (rather than an "acquisition" mechanism (contract)), in which two types of NIH programmatic involvement with the recipients should be 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 award 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 the NIH as defined below.

Definitions:

NIH Program Official

A NIH Program Official (PO) will provide the standard programmatic oversight and stewardship of the projects, including review of pre-award and award documents/requirements, review of progress reports and budgets, approval of changes in scope, budget allocation or aims, and any other programmatic issues that may arise. The PO will serve as anex officiomember of the External Advisory Committee.

NIH Project Scientist

One or more NIH Program Staff will serve as Project Scientist (PS), to monitor progress in scientific aims, identify possible collaborations with other NIH funded initiatives, review of milestones and other scientific issues, and oversee collaborative projects amongst recipients. The PS will serve as a scientific representative of the NIH to the investigators in accordance with policies and procedures of the cooperative agreement mechanism. The PS will provide NIH scientific programmatic involvement with the recipient that is anticipated during the performance of the activities supported by this Cooperative Agreement, including review of milestones. The PS will work closely with the PD/PI to maximize progress towards the goals of the project and the program and will serve as a voting member of the External Advisory Committee.

Roles and Responsibilities:

The PD(s)/PI(s) will have the primary responsibility for the following activities:

• Organize and host necessary annual scientific or programmatic meetings
• Advertise the resources available to the community through outreach activities
• Assemble the External Advisory Committee and participate in EAC activities
• Manage and coordinate project activities scientifically and administratively at the recipient institution and with any collaborating institutions
• Ensure that all data and information are disseminated according to the FAIR principles; that is data and information should be identifiable and annotated with metadata including data quality and assurances
• Ensure that all data and information involving human subjects has the appropriate security and clearances
• Wherever possible, adhere to the Open Science Initiative, to guarantee the right of others to read, redistribute, modify, and freely use any software.
• Update goals and milestones at the time of award and provide summaries of progress toward those goals, including the Project Management Plan,at least yearly, as requested by NIH. The milestones will be reviewed annually (and at other times, if necessary), and new milestones will be negotiated, as needed by working with the Project Scientist as appropriate.
• Participate in regular discussions with the NIH staff

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 DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

Program Official :

• Responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice
• Review the progress of the project and monitor for compliance with NIH Grants Policy;
• Make recommendations to the NIH for continued funding based on performance and compliance with the Terms and Conditions of the award;
• Conduct more frequent progress reviews, with the possibility that the recipient submit quarterly progress reports should problems arise in the conduct of the study;
• Serve as an ex officio member of any External Advisory Committee. The Program Official will not have voting rights on the External Advisory Committee.

Project Scientist :

• Participate in the process of coordinating collaborative project efforts and setting priorities;
• In consultation with the program officer, provide advice in the development of operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
• Serve as a voting member of any External Advisory Committee or Steering Committee as a representative of the NIH extramural staff;
• Serve as a liaison to the NIH, and as an information resource for the recipients about related research activities;

Areas of Joint Responsibility include:

PD(s)/PI(s) will constitute the External Advisory Committee (EAC) and this committee is expected to consist of individuals who are not key personnel or collaborators of the key personnel of the award. The EAC meetings will include NIH staff and may include the PD(s)/PI(s) and other members of the funded project. The EAC will select one member to act as the Chair of the committee and the Chair may not be an NIH employee. The EAC will meet at least once a year. The NIH official will serve as an ex officio member of the External Advisory Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the EAC 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 DHHS regulation 45 CFR Part 16.

3. 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.

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 FOAs 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 – 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.

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: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

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

Nsini Umoh, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1447
Email:nsini.umoh@nih.gov

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

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

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 2 CFR Part 200, 42 CFR Part 52 and 45 CFR Part 75.