Part 1. Overview Information

Key Dates

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

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

It is critical that applicants follow the 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

Purpose

This funding opportunity announcement (FOA) aims to stimulate innovative multi-disciplinary collaboration and secondary analyses of existing clinical research datasets, from two or more multi-site clinical research studies, for addressing scientific and/or clinically relevant hypotheses that have the potential to address knowledge gaps to inform future clinical trials and/or improve clinical care in research areas within the NINDS mission. For purposes of this FOA, “existing clinical research datasets” refers to datasets from clinical trials, natural history studies, and / or comparative effectiveness research studies but excludes “mechanistic clinical studies” and “basic experimental studies of humans” (for definitions see https://grants.nih.gov/grants/guide/notice-files/NOT-NS-18-011.html and https://grants.nih.gov/grants/glossary.htm#BasicExperimentalStudieswithHumans, respectively). This FOA will support the harmonization, curation and analyses of datasets from two or more multi-site clinical research studies to conduct additional secondary analyses; it will not support the collection of new data.

Background:

The substantial investments in clinical research from research participants, investigators, clinical staff, and funding agencies led the National Academy’s Institute of Medicine to recommend that clinical data be shared globally (“Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk” Institute of Medicine (U.S.), Eds., 2015), and the International Committee of Medical Journal Editors concluded that it is an “ethical obligation” to share clinical trial data, provided it is done responsibly (Taichman et al., 2016; https://doi.org/10.1371/journal.pmed.1001950). NIH encourages data sharing wherever possible, and has made significant investments in developing tools and resources to conduct large scale data science through initiatives such as the Big Data to Knowledge (BD2K) Centers, which provides tools spanning the data landscape, including metadata development, harmonization, processing, and analyses. Subsequently, NIH has recently developed a Strategic Plan for Data Science which outlines priorities aimed at modernizing the biomedical research data ecosystem. One such goal is to improve the ability to capture, curate, validate, store, and analyze clinical data for biomedical research.

The NINDS directly supports activities to improve data aggregation and secondary analyses through the development and use of common data elements (CDEs) to improve data harmonization, and by making Phase 3 clinical datasets available through the NINDS archived clinical trial datasets. Additionally, many datasets and samples from NINDS funded clinical studies are available through data resources including but not limited to: 1) Traumatic Brain Injury (Federal Interagency TBI Research (FITBIR): NOT-NS-17-029; 2) Parkinson’s Disease, Lewy Body Dementia and Parkinsonisms (Parkinson’s Disease Biomarkers Program Data Management Resource (PDBP DMR)): NOT-NS-11-020). NINDS funded datasets are also available through the Rare Diseases Clinical Research Network and the Accelerating Medicines Partnership in Parkinson's Disease (AMP PD).

This FOA is designed to support the curation and analysis of combined existing clinical research datasets. Secondary analysis of existing clinical research datasets from more than one study is infrequent in neurological disorders and conditions due to the challenges of cross-project harmonization and curation. Combining data from two or more separate studies requires significant effort, expertise, and assessment in order to determine if datasets are compatible for additional analyses. For example, two studies may use the same data dictionaries, and therefore be harmonized; yet, in-depth review of study protocols and data collection practices may reveal differences that alter or confound interpretation. Data curation improves overall data quality through careful review of processes and procedures related to data collection, documentation, and interim analyses that can identify potential differences in administration, collection, procedural differences, scoring / measurement, and / or missing data. NINDS acknowledges that for pooled analyses to be possible, studies must be able to do the critical, yet time and labor-intensive effort of curating data across studies to determine where there is sufficient compatibility for aggregated analyses. As a consequence, this initiative provides funding for multidisciplinary teams that include extensive clinical, statistical and data informatics expertise to do secondary analyses of existing clinical research datasets from multiple multi-site projects. Applicants are encouraged to apply with applications that seek to address broad issues of heterogeneity related to demographics (age, race, ethnicity, gender, socio-economic status, and cultural diversity), disease state, point of care, and/or clinical protocols (e.g. treatment, primary outcome, and differences in care conditions, etc.). Although valuable in their own right, re-analysis of individual datasets is not appropriate for this opportunity.

Specific Research Objectives:

Applications to this FOA are expected to harmonize, curate and analyze data from two or more multi-site existing clinical research to promote discovery and / or validation of scientific or clinically-relevant hypotheses that 1) were beyond the scopes of the original studies, 2) would not be possible using a single-site or single multi-site dataset , 3) validate or expand clinically significant findings, and / or 4) utilize new or advanced methods of analysis that allow exploration of important disease-related scientific or clinical questions. It is expected that the data used will primarily consist of cross-sectional or longitudinal individual participant level data (i.e. primary data). This FOA will not support the collection of new data.

The investigative team must include clinical subject matter expertise as well as statisticians and bioinformaticians/data scientists. Teams should include investigators involved in the original data acquisition either as part of the investigative team or as consultants. Inclusion of trainees and young investigators on the investigative team is also highly encouraged. This multi-disciplinary team-science strategy should encourage cross-fertilization of knowledge and utilize appropriate subject matter expertise for interrogating data. To ensure maximal value of the project, applicants to this FOA are expected to include open-source cataloging of the processes and tools used for harmonization, curation, and analysis, as well as provide a sustainable plan for controlled-access to the curated datasets.

Examples of potential research topics include, but are not limited to:

• Validation of diagnostic and/or prognostic models of outcome
• Comparative effectiveness hypotheses
• Mediation analyses of biological, cultural and environmental factors that affect treatment response or course of disease
• Evaluation of biomarker and clinical outcome assessments (COAs) validity in new populations and/or new context of use
• Discovery or validation of multi-domain clinical and/or biological measures for diagnosis, prognosis and/or treatment response using existing genetic and biological samples along with clinical and physiological assessments
• Extended characterization or validation of natural history disease course
• Novel methods for improving patient stratification
• Projects which include a focus on health disparities and inequities in neurological disease, healthcare, and health outcomes in disparate populations, including racial and ethnic minorities, the geographically disadvantaged, sex and gender minorities, and others who have been historically underserved, socioeconomically disadvantaged, marginalized, or adversely affected by persistent inequality.

Data Harmonization and Curation Resources:

In lieu of preliminary data, applications should provide sufficient information demonstrating that the datasets proposed to be combined are, or can be, sufficiently harmonized to proceed with curation and analyses. Investigators are encouraged to make use of existing resources, tools and training from the NIH’s BD2K Centers (https://commonfund.nih.gov/bd2k/centers), such as:

• The Center for Expanded Data Annotation and Retrieval (CEDAR) provides a computational ecosystem for development, evaluation, use, and refinement of biomedical metadata; https://more.metadatacenter.org/tools-training
• Center for Causal Discovery (CCD) develops computational methods known as causal discovery algorithms that can be used to discover causal relationships from a combination of observational data, experimental data, and prior knowledge; https://www.ccd.pitt.edu/tools/
• Big Data for Discovery Science (BDDS) provides software tools and data resources developed for the management, manipulation, and mining of large-scale biomedical data along with education and training resources; https://bd2k.ini.usc.edu/tools/.

Applications are expected to include plans to harmonize data, wherever appropriate, to the NINDS Common Data Elements (CDEs) for both outcome and non-outcome variables. CDISC standards should also be incorporated where applicable. Investigators are also encouraged to review and incorporate other relevant validated consensus standards to improve overall harmonization with other sources. Standards should be cited, and the selection should be justified.

Reproducibility and 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.

Rigor: The research strategy should clearly describe how the application will utilize a rigorous design, execution, and interpretation of the proposed studies. NINDS encourages investigators, whenever possible, to address these elements directly in their applications. Investigators are urged to discuss these issues with Scientific/Research staff prior to submission of applications (see: NOT-OD-16-011 and NOT-OD-18-228).

Go/No-Go Criteria: Applicants should demonstrate feasibility of the planned analyses and hypotheses testing based on data harmonization and curation, as well as quantitative curation standards that establish the Go/No-Go Criteria needed to move from curation and harmonization in the R61 phase into the R33 secondary analysis phase.

Applications Not Responsive to this FOA

The following types of activities remain outside of the scope of this FOA, and applications proposing such activities will be considered non-responsive to this FOA and will be withdrawn without review:

• New data collection
• Studies using non-human animal models
• Studies using data from a single clinical research study
• Multiple single-site clinical research studies
• Studies of harmonization, curation, and analysis where the primary data source is Electronic Health Record (EHR) data
• Studies of harmonization, curation, and analysis where the primary data source is metadata

Applicants are encouraged to contact the Scientific/Research staff listed below for clarification regarding the scope of this funding opportunity.

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 Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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

Non-domestic (non-U.S.) components of U.S. Organizations are 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 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:

Christine Swanson-Fischer, PhD
Telephone: 301-496-5680
Email: [email protected]

Page Limitations

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.

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.

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.

Other Attachments:

1. Provide a description of any relevant policies governing the proposed datasets and how the project will comply. This attachment should not exceed 3 pages and should be entitled "Dataset policies.pdf".
2. Where possible, provide a copy of the informed consent document for each proposed clinical dataset.  This attachment should be entitled “Informed consent.pdf”.

SF424(R&R) Senior/Key Person Profile

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

As team members with these areas of expertise are required, please highlight how the Research Team has the appropriate expertise (without duplicating information in the biosketches) in:

• Clinical Neurology and Epidemiology
• Biomarker, Functional genomics, neuroimaging, neuropathology (where appropriate)
• Curation and harmonization of complex clinical and endophenotypic data
• Computational biology, Bioinformatics
• Statistics

R&R Budget

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

The cost for running software and services in the cloud environment (if appropriate) may be included in the budget.

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: Provide the overall goals or hypothesis of the entire project and list separate Specific Aims to be accomplished: briefly outline the methods proposed and summarize the expected outcome. Briefly describe how the hypotheses being tested are unique from, are a significant advancement of original studies hypotheses, or provide a unique opportunity to validate or expand the knowledge gained in the original studies. Within the Specific Aims section, include headers titled R61 Phase Specific Aims and R33 Phase Specific Aims. Under each header, state the specific aims of the efforts for each phase of the study. Since the goal of the R61 phase of this FOA is data harmonization and curation, hypothesis testing, per se, may not be applicable in the R61 phase.

Premise: Describe the overall scientific or clinical need and significance of the research question and how it may impact future clinical trials or clinical care. Applicants must propose to harmonize, curate and analyze data from two or more multi-site existing clinical research datasets and justify the need for the combined cohort, including relevance and necessity of any non-U.S. study populations. Provide feasibility evidence that the multi-site existing clinical research datasets to be combined have been, or can be, harmonized. Include evidence that the datasets to be combined were collected in a rigorous and unbiased way with sufficient quality assurances to assure value, (e.g. blinding, randomization, documentation of data collection practices, quality checks and version control).

Collaboration: Applicants must form multidisciplinary teams that consist of the relevant expertise to accomplish the goals outlined in the research plan. Teams should include, at minimum, a mix of clinical, statistical and informatics and/or computational experts. Additionally, applications should include plans for incorporating trainees and/or young investigators into the research team to facilitate cross-fertilization of data-science and scientific/clinical research expertise in the next generation of researchers.

Research Plan

R61 Phase - Data Curation and Harmonization

Describe the goals, processes, and deliverables of data harmonization and curation, and operational definitions of "harmonization" and "curation" must be provided. Descriptions of the data types, provenance, and accessibility must be provided for each of the multi-site existing clinical research datasets including verification that the data to be harmonized, curated, and analyzed consist primarily of individual participant level data.

The data harmonization component should demonstrate the feasibility of the project; for example, by providing evidence that the projects’ data dictionaries (nomenclature) are aligned to validated consensus standards including use of all applicable NINDS CDEs and CDISC standards and that relevant outcome assessments or diagnostics protocols have sufficient similarity to be harmonized. A plan for obtaining or retrieving the relevant datasets should also be addressed with letters of support provided where necessary, including evidence that the datasets were collected with the appropriate consent forms to allow for the proposed studies. The data curation component should provide detailed descriptions of how the datasets will be interrogated for quality assurance and reviewed for reliability, including, but not limited to security, user access documentation, data entry quality assurance checks, audit trails, and data version control. Clear data quality criteria must be included that provide justification for inclusion, imputation, and exclusion of relevant data points and data elements. Successful applications will include in-depth reviews of study protocols and data collection practices to identify where differences may alter or confound interpretation, along with plans to address such issues. Applicants should include a description of the intended curation pipeline, ensuring it is documented, reproducible and uses approaches/code/software designed for interoperability. Software, code/scripts, tools, and metadata standards developed for harmonization and curation should be shared (e.g., using open-source software code repository) and should consider interoperability with other sources. Metadata created during the harmonization and curation process must also be shared. Applicants should request appropriate staff and computational time to allow for unforeseen challenges that may arise.

R33 Phase - Secondary Analyses

Describe the analysis/es plan, and directly address the risk for spurious findings from aggregated datasets. Applicants should include sufficient background to demonstrate how the scientific or clinically relevant hypotheses are unique from, or will sufficiently expand upon, the studies where the data originated, as well as how the combined cohort provides a unique opportunity to test the research question(s). Additionally, applications should discuss and report effect size (e.g., percentage of variance explained) relative to the expected variance due to differences in data collection practices. A description of the approaches for dealing with missing data, and data outliers should also be included. Applicants are strongly encouraged to pre-register hypotheses, aim(s), design(s), and plans for statistical analyses to journals for peer review prior to beginning their project. All applicants are strongly encouraged to make use of the tools and resources available through the BD2K Centers wherever possible.

Timeline and Milestone Plan:

• Transition from the R61 to the R33 phase is contingent upon the successful completion of R61 proposed milestones. The specific milestone(s) proposed in the application will depend on the goals of the application and the accomplishments necessary in the R61 phase for advancement into the R33 phase. Milestones and go/no go criteria 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 R61/R33 application.
• Milestones should be proposed for completion at the end of the R61 phase. 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 not only in peer review but also in consideration of the awarded project for funding of the R33 phase. A discussion of the curation and harmonization goals relative to the progress of the R61 phase and implications of successful transition to the R33 phase for performing secondary analyses should be included.
• 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.

Letters of Support:

• Applicants should include letters of support from consultants, contractors, and collaborators.
• If an application plans to utilize the infrastructure or resources of existing projects, whether funded by the NINDS, other governmental or non-governmental entities, letters of support detailing the terms of collaboration and data sharing must be included.
• For projects that propose analysis of data which are not currently controlled by the PD/PI, a letter of support confirming the availability of the data and the willingness and permissibility of the original investigator(s) to share the data is required.

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.

Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment of the Overall Component in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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

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 applications, regardless of the amount of direct costs requested for any one year must describe the following: - How and when the protocols, related tools, metadata, software and/or code used for harmonization, curation and analyses will be made available (open access is expected). - How and where the final curated datasets will be located. Where possible (e.g. permitted by appropriate consent), the harmonized dataset should be deposited into an NIH appropriate data repository to be made widely available to the scientific research community. If the data are privately held, information regarding the location, duration, and process for requesting access to the data must be described. In such cases, a letter of support from the manager of the data archive should be included in the application indicating that the archive will accept the dataset. - Applicants are expected to address how the proposed studies will adhere to the responsible for adhering to any policies governing access to and disposition of study datasets consistent with the NIH Data Sharing Policy and Implementation Guidance, the NIH Genomics Data Sharing Policy (NOT-OD-14-124) and the NIH Notice for Use of Cloud Computing Services for Storage and Analysis of Controlled-Access Data Subject to the NIH Genomic Data Sharing Policy (NOT-OD-15-086), as applicable. Applicants should also implement the NIH security best practices and provisions to protect the privacy and confidentiality of research participants and prevent unauthorized access to data.

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 Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix:

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

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

Applications must include the informed consent form (ICF) for datasets which are not yet publicly available

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.

Section 3 - Protection and Monitoring Plans 3.1 Protection of Human Subjects

The application must include sufficient information to assure that the data to be used are in accordance with the patient informed consent forms, as well as any local, national or regional laws and policies.

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 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.

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 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.

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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.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide

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.

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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).

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.

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), 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.

• 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.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 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:

• Federal wide 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 will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their 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. 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.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/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 religious nondiscrimination laws and 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.”

Not applicable

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.

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 the threshold.  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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 Condition 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: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Christine Swanson-Fischer, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: (301) 496-5680
Email: [email protected]?

Ishwar Chandramouliswaran
Office of Data Science Strategy (ODSS)
Email: [email protected]
 

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
E-mail: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Section VIII. Other Information

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

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