Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Funding Opportunity Title
Validating digital health technologies for monitoring biomarkers in ADRD clinical trials (R61/R33 - Clinical Trials Optional)
Activity Code

R61/R33 Exploratory/Developmental  Phased Award

Announcement Type
New
Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Aging (NIA)

Related Notices
  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Notice of Funding Opportunity (NOFO) Number
RFA-NS-24-026
Companion Funding Opportunity
None
Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)
93.853, 93.866
Funding Opportunity Purpose

The purpose of this RFA is to encourage development and validation of digital monitoring biomarkers and digital functional/behavioral assessments for monitoring symptoms or aspects of Alzheimer's Disease Related Dementias (ADRD) that impact quality of life. In this phased mechanism, applicants are expected to use one or more existing wearable digital health technologies (DHTs) and develop and verify the analysis/algorithms or software to accurately detect and measure the physiological or functional aspects of interest, and then in the second phase, conduct a prospective longitudinal study to validate the measurements of the biomarker or functional/performance outcome in two or more ADRD populations, in real world conditions.  The longitudinal studies should include participants from communities that are historically underrepresented in clinical studies including racial and ethnic minorities, individuals in rural populations, and individuals with limited English proficiency. Outreach activities may be included in the R61 phase in preparation for successful recruitment and retention in the R33 phase.

Key Dates

Posted Date
August 02, 2023
Open Date (Earliest Submission Date)
October 17, 2023
Letter of Intent Due Date(s)

September 17, 2023

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
November 17, 2023 Not Applicable Not Applicable March 2024 May 2024 July 2024

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

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

Expiration Date
November 18, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background:

In 2011, the National Alzheimer's Project Act (NAPA) allocated resources "to prevent and effectively treat Alzheimer's by 2025." Since then, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) have held multiple research summits to assess the needs and opportunities relevant to this goal for Alzheimer's Disease (AD) and Alzheimer's Disease Related Dementias (ADRD). In particular, the NINDS has convened expert panels in 2013, 2016, 2019 and 2022, that were tasked with recommending research priorities for advancing the state-of-the-science for the Alzheimer's disease (AD) and Alzheimer’s disease-related dementias (ADRD) by 2025. ADRD are defined as Frontotemporal Degeneration (FTD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), Lewy Body Dementias (LBD) and Multiple Etiology Dementias (MED).

Individuals with ADRD can have many physiological changes that lead to a variety of symptoms and changes in function that negatively impact quality of life but may be difficult to accurately monitor and track through standard clinical outcome assessments. Examples include sleep disorders, such as idiopathic REM sleep behavior disorder (RBD) in LDB, and insomnia and daytime sleepiness in FTD. Likewise, mobility, autonomic dysfunction such as orthostatic hypotension leading to postural instability and falls, as well as gastrointestinal issues, all negatively impact quality of life, but are difficult to accurately track and quantify when relying on self-report or caregiver reports. Use of digital health technologies (DHTs) to enable monitoring in clinical trials as exploratory or secondary endpoints is rapidly increasing. Advantages of using digital endpoints in clinical trials are numerous, including enabling higher frequency longitudinal data collection in real world conditions and reducing the burden of participation in clinical trials, which can increase participant recruitment and retention.  However, like all biomarkers and clinical assessments, demonstrating utility and reliability requires extensive fit-for-purpose validation. As described in the FDA’s draft guidance “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations”, evidence must include verification that the device can accurately, and reliability measure the physiological, functional or behavioral characteristics that make up the biomarker(s) or assessments of interest, and also establish the statistical relationship between the changes in the biomarker or assessment with a clinically meaningful change in how the patient feels, functions, or survives.  Although Digital Health Technologies (DHTs) are broadly defined as “a system that uses computing platforms, connectivity, software, and/or sensors for healthcare and related uses”, the focus of this funding opportunity is on developing digital biomarkers and performance/functional assessments from data generated from wearable sensor-based devices.

Definitions:

  • Digital Health Technologies (Wearables/Devices/Technologies): a system that uses computing platforms, connectivity, software, and/or sensors for healthcare and related uses.
  • Clinical Outcome Assessment (COA): a measure that describes or reflects how a patient feels, functions, or survives. Types of COAs include:
    • Patient-reported outcome (PRO)
    • Observer-reported outcome (ObsRO)
    • Clinician-reported outcome (ClinRO)
    • Performance outcome (PerfO)/Functional outcome
  • Biomarker: a defined characteristic that can be measured as an indicator of normal biological processes, pathogenic processes or responses to an exposure or intervention, including therapeutic interventions
  • Digital Biomarker: The term “digital biomarker” is widely used to mean assessments that include both biological processes (such as changes in heart rate or galvanic skin response) as well as performance/functional/behavioral assessments (such as measurements derived from accelerometers). Both digital biomarkers and digital performance/functional assessment are within scope of this NOFO.
  • Monitoring Biomarker: As defined in the Biomarkers, EndpointS, and Other Tools (BEST) Resource (https://www.ncbi.nlm.nih.gov/books/NBK338448/), a monitoring biomarker is one that is measured repeatedly for assessing status of a disease or medical condition or for evidence of exposure to (or effect of) a medical product or an environmental agent.
  • Concept: the aspect of an individual’s clinical, biological, physical or functional state, or experience that the assessment is intended to indicate or reflect.
  • Context of Use (COU): is a statement that fully and clearly describes the way the biomarker is to be used and the biomarker-related purpose of the use. Considerations involved in defining the COU include the biomarker category, modality, method of detection, clinical population characteristics, and unmet need for the new biomarker and type of biomarker.

Research Objectives and Scope:

This NOFO uses a phased R61/R33 mechanism. Applications must include both the R61 and R33 phases.  Partnerships between device manufactures and academics are encouraged to consider and plan for using the verification and validation studies supported through this NOFO to help obtain regulatory approval such as commercialization of associated software or dissemination of open-source analysis packages.  The purpose of the R61 phase is to develop and verify the accuracy of the analysis of the data from the DHT(s) to detect, measure, and track, changes in the physiological and functional/behavioral aspects of interest (verification of the device(s) accuracy and reliability) against gold standard assessments/technology. Study participants should include representatives from two or more ADRD populations as well as any other controls needed. The R33 phase should include a prospective longitudinal validation study in a large representative cohort of individuals with the ADRD conditions of interest. Studies may wish to leverage existing clinical trials or may propose a clinical trial (provided the primary intent is validation of the biomarker, not assessment of the safety or efficacy of the intervention).  Studies should include and justify any additional biomarkers or clinical assessments used to validate the sensitivity and specificity of the digital biomarkers/assessments against. Examples of activities that may be supported in each phase are included below. It is a priority to include recruitment and retention of participants from communities that are historically underrepresented in clinical studies including racial and ethnic minorities, individuals in rural populations, and limited English proficiency, therefore applicants are encouraged to consider including outreach activities in the R61 phase to enable successful recruitment in the R33 phase. 

First Phase (R61) activities may include, but are not limited to:

  • Verification and validation pilot studies to optimize the algorithms to measure the concept of interest against gold standards in the target patient populations.
  • Evaluate factors that may interfere with the precision and accuracy of the measurement
  • Evaluate and compare DHTs for selection in the R33 validation study
  • Develop user-informed consent and training materials for the R33 phase with input from individuals with lived experience and representatives from diverse communities
  • Conduct outreach activities and establish collaborations with communities that are historically underrepresented in clinical studies including racial and ethnic minorities, individuals in rural populations, and individuals with limited English proficiency, as part of preparation for successful recruitment and retention in the R33 phase validation study
  • Establish the final statistical analysis and data management plans for the R33 phase

Second Phase (R33) activities may include, but are not limited to:

  • Conduct a prospective longitudinal study to determine the statistical relationships between the digital monitoring biomarker or performance/functional assessment with established biomarkers, clinical outcome assessments, and consumer/patient informed quality of life metrics.
  • Evaluate the digital biomarker or digital functional/behavioral assessment’s response to a therapeutic or behavioral intervention
  • Submit a letter of intent to FDA Biomarker or COA Qualification Program

Go/No-Go Milestones:

Transition from the R61 to the R33 phase is contingent upon the successful completion of Go/No-Go milestones. Milestones must be proposed in the application, and should be clearly defined, quantifiable, and scientifically justified to assess progress in the R61 phase. Milestones must include the minimum acceptable sensitivity, specificity, accuracy, and precision of the detection and measurement of the digital biomarkers or digital performance/functional assessments, as well as milestones documenting successful completion of other activities needed to demonstrate feasibility and readiness for the R33 phase, in particular, activities for successful recruitment and retention.  

Rigor and Transparency:

NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency (https://grants.nih.gov/policy/reproducibility/guidance.htm) and provides additional guidance to the scientific community (https://www.ninds.nih.gov/Funding/grant_policy). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.

Intellectual Property (IP)

The program strongly encourages the recipients and/or their collaborators to establish an IP agreement with the digital health technology manufacturers for the algorithms and/or related software used to detect, measure and monitor the digital biomarkers or performance/functional assessments (see instructions on attachment or letters to address IP issues in Section IV). Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the development process. Investigators are expected to work closely with technology transfer officials at their institution to ensure that patent filings, and all other necessary intellectual property arrangements are completed in a timely manner. 

Non-Responsive (Out of Scope) Studies:

  • Studies where the primary intent is to develop the device(s) to be used rather than validating the data analysis and interpretation from the device(s).
  • Studies focused on patient reported outcomes, observer-reported outcomes, or clinician-reported outcome assessments.
  • Natural history studies aimed at understanding disease pathophysiology, genetic, or epigenetic mechanisms without digital biomarker/functional assessment verification and validation
  • Studies where the primary intent is to develop or test a therapeutic or behavioral intervention to assess safety or efficacy.
  • Studies that do not include testing in two or more ADRD populations 
  • Incomplete applications (applications with only the R61 or R33 phase, or applications missing the Go/No Milestones)

Non-responsive studies will be administratively withdrawn prior to review.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Funds Available and Anticipated Number of Awards

NIH intends to commit the following amounts in FY24: $3,000,000 total budget to fund up to two awards contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Direct Costs cannot exceed $1,000,000 per year and need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period with the R61 phase be 1-2 years and the R33 phase should be 2-3 years. The maximum project period is 5 years. 

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

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

Other

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

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

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

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

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

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

The letter of intent should be sent to:

Carol Taylor-Burds, PhD
Telephone: 301-451-4551
Email: carol.taylor-burds@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Intellectual Property (IP) Strategy (Required, 3 pages maximum):

Applications that exceed this limit or do not include this attachment will be withdrawn. This attachment should be entitled "IP Strategy.pdf". Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

A goal of this program initiative is to advance research towards the development of products that will benefit the public. Accordingly, applicants should describe the IP landscape of measurements derived from data collected from the digital health technology (DHT) device(s). This should include any known constraints that could impede the development of the algorithms and any associated software (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent and/or on the market, etc.) and how these issues could be addressed as appropriate and consistent with achieving the goals of the program

  • If the applicant proposes using a device or technology whose IP is not owned by the applicant's institution, the applicant should address any questions that may constrain or impede its ability to operate and move the technology forward consistent with achieving the goals of the program.
  • Applicants should include a letter of support from the entity that owns the IP indicating whether the entity will provide the device or technology, if there are any limits on the studies that can be performed with that device or technology, and if there is agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.
  • If patents pertinent to the measurement algorithms and/or associated software are being developed under this application and have been filed, the applicants should indicate the details of filing dates, what types of patents are filed, application status, and associated United States Patent Office (USPTO) links, if applicable.
  • Applicants should also discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe how IP will be shared or otherwise managed, and the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions.
SF424(R&R) Senior/Key Person Profile

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.

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 a concise (1 page) description of the aims for both the R61 and R33 phases of the project.

Research Strategy (applications must address all of the following elements):

Significance and Clinical Impact 

Describe why the digital biomarker(s) or digital performance/functional assessments to be developed and validated are needed for use in future clinical trials for the two or more ADRD conditions of interest; address why they would be valuable secondary or primary endpoints in clinical trials to advance therapeutic development, behavioral/lifestyle interventions, and/or comparative effectiveness research. Explain how the verification and validation studies supported through this RFA would be used to obtain regulatory approval such as commercialization of associated software or dissemination of open-source analysis packages for use in future clinical trials.

Premise and Biological Rationale 

Explain what is known about the relationship between the underlying physiology of the ADRDs of interest with the concept of interest that the digital biomarker or digital performance/functional assessment is intended to measure.

Choice of Digital Health Technology (DHT) 

Justify the selection and choice of the DHT(s) to be used to measure the digital biomarker(s) or performance/functional assessments including any relevant performance characteristics of the device(s) and any preliminary data (if available) supporting their ability to measure the concept(s) of interest.

Approach

Describe and justify the approach and study designs for both the R61 and R33 phases which should include, but are not limited to:

R61 phase

  • Explain the approach to detecting and optimizing the measurement of the digital biomarker(s) or performance/functional assessments from the data generated by the wearable DHTs and the approach for verification of these biomarkers against established standards
  • Include a plan for evaluating factors that may interfere with the precision and accuracy of the measurement(s) and (if applicable) how the results might inform or modify the R33 study design
  • Any activities for developing the consent and training materials for the R33 phase, including how individuals with lived experience that bring diverse perspectives will be involved as part of the research team
  • Any activities to establish or strengthen engagement with communities that are historically underrepresented in clinical studies including racial and ethnic minorities, rural populations, and populations with limited English proficiency, in preparation for successful recruitment and retention in the R33 phase validation study (evidence of successful community engagement should also be proposed as Go/No-Go milestones)
  • Any contingency plans that address how the results of the R61 phase may be used to refine the R33 phase study design and statistical analysis plan for the R33 phase validation study

Go/No-Go Milestones: 

  • Clear quantitative Go/No-Go milestones must be included in the research plan. These should include, but are not limited to, the minimally acceptable sensitivity, specificity, accuracy and precision of the DHTs to detect and measure the digital biomarkers or performance/functional assessments of interest. Feasibility  metrics such as development of recruitment, consent and training materials, and/or evidence of having established partnerships with underrepresented communities may also be proposed to provide evidence of the readiness for the R33 longitudinal study. 

R33 phase:

  • Describe and justify the study design of the longitudinal prospective validation study including the statistical design and assumptions
  • Describe and justify the primary and secondary endpoints that the digital biomarkers and/or digital functional assessments will be validated against
  • Describe and justify the plans for blinding, randomization and what controls will be included
  • Without duplicating information already provided in the PHS Human Subjects and Clinical Trial (HSCT) information, describe and justify the recruitment and retention plans, which should include a discussion of the availability of participants for the proposed study and the ability of enrollment sites to recruit and retain the proposed number of participants meeting the eligibility criteria, including women and racial and ethnic minority participants, as applicable
  • Describe any established standard protocols and data collection standards to be used (such as CDISC: https://www.cdisc.org/, and the NINDS Common Data Elements: https://www.commondataelements.ninds.nih.gov/#page=Default)

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. 

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

  • All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing 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.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application guide

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

Partnerships between device manufactures and academics are encouraged (but not required) to consider and plan for using the verification and validation studies supported through this NOFO to help obtain regulatory approval such as commercialization of associated software.  

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this NOFO:

  • If validated, is  the digital biomarker(s) or digital performance/functional assessments likely to  meet an unmet need   as a primary or secondary endpoint in future clinical trials to advance therapeutic development, behavioral/lifestyle interventions, and/or comparative effectiveness research? 

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

In addition, for applications involving clinical trials

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

Innovation

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

In addition, for applications involving clinical trials

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

Specific to this NOFO:

  • If validated,  is the proposed digital biomarker and/or digital performance/functional assessment likely to enable  innovation in future clinical research studies?


 

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

Specific to this NOFO:

R61 phase approach

  • Is there an appropriate plan for evaluating and controlling for factors that may interfere with the precision and accuracy of the measurement(s)? 
  • Does the application provide adequate contingency plans that address how the results of the R61 phase may be used to refine the R33 phase study design and statistical analysis plan for the R33 phase validation study?
  • Are there appropriate plans to establish or strengthen engagement with communities that are historically underrepresented in clinical studies including racial and ethnic minorities, rural populations, and populations with limited English proficiency, in preparation for successful recruitment and retention in the R33 phase validation phase?

Go/No-Go Milestones and timeline

  • Does the application sufficiently  justify the minimum acceptable sensitivity, specificity, accuracy, and precision needed to be achieved by the digital biomarker(s)/digital functional assessments to meet the requirements needed for the R33 phase longitudinal validation study?
  • Are the milestones and timeline appropriate to support feasibility of the R33 phase? 

R33 phase approach

  • Does the application sufficiently describe and justify the study design of the longitudinal prospective validation study including the overall statistical design and assumptions?
  • Are the primary and (if applicable) secondary endpoints the biomarker is being validated against, sufficiently  justified and appropriate? 
  • Does the application adequately describe and justify the plans for blinding, randomization and use of controls?
  • Does the application adequately describe and justify the recruitment and retention plans which should include a discussion of the availability of participants for the proposed study and the ability of enrollment sites to recruit and retain the proposed number of participants meeting the eligibility criteria, including women and racial and ethnic minority participants, as applicable?
  • Are there appropriate plans for standardization and harmonization of the data described and appropriate?
  • Are the plans for testing in two or more ADRD populations included and appropriate?  

Environment

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

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

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

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

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

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.

Go/No-Go Milestones

Will successful completion of the proposed milestones provide confidence that the team will be able to successfully implement the R33 phase and achieve the goals within the timeline of this grant mechanism? Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps? 

Study Timeline

Specific to applications involving clinical trials

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

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

Resubmissions

Not Applicable 

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Intellectual Property

 Are intellectual property (IP) agreements in place or likely to be in place by the time of an award?

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (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 NOFO.

Applications will be assigned on the basis of established PHS referral guidelines to NINDS. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the NINDS or NIA 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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

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

Cooperative Agreement Terms and Conditions of Award

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 NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

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

Scientific/Research Contact(s)

Carol Taylor-Burds, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-451-4551
Email: carol.taylor-burds@nih.gov

Yuan Luo
NATIONAL INSTITUTE ON AGING (NIA)
Phone: 301-496-9350
E-mail: luoy2@mail.nih.gov

Peer Review Contact(s)

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

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

Financial/Grants Management Contact(s)

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

Philip Smith
NATIONAL INSTITUTE ON AGING (NIA)
Phone: 301-555-1212
E-mail: philip.smith2@nih.gov

Section VIII. Other Information

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

Authority and Regulations

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

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