The purpose of this proposed Notice of Funding Announcement (NOFO) is to support development of biomarkers or clinical outcomes derived from digital health technology (DHT) for use in clinical trials for remote monitoring as primary or secondary endpoints. To improve clinical impact, increase statistical feasibility, and promote standardization, applicants will be expected to develop and test the digitally derived assessments in populations from at least three different diseases or conditions. Partnerships with non-profit patient advocacy organizations will be required.

PAR-25-170: Digital Health Technology Derived Biomarkers and Outcome Assessments for Remote Monitoring and Endpoint Development (UG3/UH3 - Clinical Trial Optional)

Posted Date: November 13, 2024 Open Date (Earliest Submission Date): January 21, 2025 Expiration Date: June 23, 2026

Updates:

• March 31, 2025: This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.
• December 13, 2024: Notice of Participation of the National Institute on Aging in PAR-25-170, "Digital Health Technology Derived Biomarkers and Outcome Assessments for Remote Monitoring and Endpoint Development (UG3/UH3 - Clinical Trial Optional)". See Notice NOT-AG-24-083.
• April 4, 2024: Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084.
• 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.

Part 1. Overview Information

Participating Organization(s):

• National Institutes of Health (NIH)

Components of Participating Organizations:

• National Institute of Neurological Disorders and Stroke (NINDS)
• National Cancer Institute (NCI)
• National Institute on Aging (NIA) - Participation added December 13, 2024 (NOT-AG-24-083)

Other Participating NIH Offices (may co-fund):

• Office of Behavioral and Social Sciences Research (OBSSR)

Funding Opportunity Title: Digital Health Technology Derived Biomarkers and Outcome Assessments for Remote Monitoring and Endpoint Development (UG3/UH3 - Clinical Trial Optional)

Activity Code: UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type: New

Related Notices:

• March 31, 2025 - Update to align with agency priorities.
• December 13, 2024 - Notice of NIA Participation (NOT-AG-24-083).
• April 4, 2024 - Grant Application and Review Changes (NOT-OD-24-084).
• August 31, 2022 - Genomic Data Sharing Plans (NOT-OD-22-198).
• August 5, 2022 - NIH Data Management and Sharing Policy (NOT-OD-22-189).

Funding Opportunity Number (FON): PAR-25-170

Companion Funding Opportunity: None

Number of Applications: See Part 2 Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s): 93.853, 93.399, 93.866

Funding Opportunity Purpose: The purpose of this notice of funding opportunity (NOFO) is to support rigorous development and validation of Digital Health Technology (DHT) derived biomarkers or clinical outcome assessments (COAs) for remote monitoring to fill a defined unmet clinical endpoint for interventional clinical trials. Applicants must propose to develop and evaluate the DHT enabled biomarkers or COAs in three or more diseases or conditions to increase standardization and improve clinical adoption. Applicants must also propose to conduct development studies informed by people with lived experience (PWLE) and patient advocacy organizations.

The first phase (UG3) evaluates the technical performance of the proposed DHTs with PWLE input. The second phase (UH3) supports a prospective longitudinal clinical study in representative populations to validate the DHT. Research outcomes should demonstrate how a meaningful change in the biomarkers or COAs derived from the DHT(s) can be statistically measured and quantified at the individual participant level.

Funding Opportunity Goal(s):

1. To support extramural research funded by the National Institute of Neurological Disorders and Stroke (NINDS), including basic research, understanding causes of nervous system disorders, natural course of disorders, prevention, diagnosis, treatment, drug development, neural devices, clinical trials, and training in neuroscience.
2. To expand and improve the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs to increase private sector commercialization of innovations, small business participation in R&D, and foster participation of socially and economically disadvantaged and women-owned small business concerns.

Key Dates:

• Posted Date: November 13, 2024
• Open Date (Earliest Submission Date): January 21, 2025
• Expiration Date: June 23, 2026

Application Due Dates, Review and Award Cycles:

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.

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 is required and strictly enforced.

Submission Options:

• Use the NIH ASSIST system.
• Use an institutional system-to-system (S2S) solution (check with your institution).
• Use Grants.gov Workspace.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background: There is a high unmet need for clinical endpoints that can be assessed remotely in clinical trials. Digital health technologies (DHTs), including wearable or home monitoring sensors and software-based applications, offer potential for remote assessments. These can reduce participant burden and improve sensitivity to change due to more frequent assessments. Successful development requires rigorous studies, collaboration with people with lived experience (PWLE), and understanding regulatory expectations.

The goals of this NOFO are to:

1. Encourage collaboration across disease areas to pool expertise and resources.
2. Support research to generate data for the development, analytical validation, and proof-of-concept clinical validation of DHT-derived assessments and monitoring biomarkers for use as future endpoints in clinical trials across three or more disease areas.

Research Scope and Special Requirements and Considerations:

• Partnerships: Collaboration with patient advocacy organizations and PWLE is required to inform study design, endpoint selection, and community uptake.
• Three or More Diseases/Conditions: Required to encourage standardization, collaboration, pooled resources, and successful translation.
• Unmet Need: Development and validation should fill an unmet need as primary or secondary endpoints in clinical trials (e.g., therapeutic development, rehabilitation, comparative effectiveness, preventative medicine).
• Contexts of Use (COU): Must consider the feasibility of integrating remote assessments into clinical trials as endpoints.
• Digital Health Technologies (DHT): May include wearable sensors, in-home technologies, or web-based applications.
• Community Engagement Plan: Required, outlining how communities will be engaged throughout the research process. This plan should identify relevant parties, their meaningful involvement, and justify how engagement will enhance the research and its relevance. Reference the National Academy of Medicine's strategy for assessing meaningful community engagement.
• Timeline, Annual Milestones, and UG3/UH3 Transition: Must be included, describing project decision points with quantitative metrics for go/no-go decisions. A research performance progress report (RPPR) detailing completed milestones is required for transition to the UH3 phase. Transition decisions are based on milestone achievement, readiness, feasibility, funds, and program priorities.

Appropriate Activities for Each Phase:

• First Phase (UG3; 1-2 years):

  • Device selection and analytical validation pilot studies to optimize algorithms.
  • Evaluate factors that may interfere with data precision and accuracy in real-world environments.
  • Optimize and finalize protocols for standardization, considering missing data and required wear/use time.
  • Establish final statistical analysis and data management plans for the UH3 phase.
  • Develop user-informed consent and training materials for the UH3 phase (refer to NIH guidance on informed consent for DHTs).
  • Conduct outreach and establish collaborations with underrepresented communities for UH3 recruitment and retention.
  • Obtain input from relevant regulatory agencies (e.g., FDA Critical Path Innovation meetings, CMS).

• Second Phase (UH3; 3-4 years, max 5 years combined):

  • Conduct a prospective longitudinal study to determine statistical relationships between DHT measures and established biomarkers, COAs, and quality of life metrics.
  • Evaluate the DHT measure's response to therapeutic or behavioral interventions.
  • Obtain regulatory input (e.g., FDA Drug Development Tools qualification programs).

Definitions:

• Disease/condition: A disorder of structure or function.
• Digital Health Technologies (DHT) and sensor-based digital health technology: Systems using computing platforms, connectivity, software, and/or sensors for healthcare uses (e.g., wearable sensors, mobile/app-based assessments, in-home monitoring).
• Remote assessment: Collection of data from a participant's location distant from the investigator.
• Concept of interest (COI): The aspect of an individual's state or experience the assessment is intended to indicate.
• Clinical Outcome Assessment (COA): A measure describing how a patient feels, functions, or survives (includes PRO, ObsRO, ClinRO, PerfO/Functional outcome).
• Biomarker: A measurable characteristic indicating normal biological processes, pathogenic processes, or responses to exposure/intervention.
• Monitoring Biomarker: Measured repeatedly for assessing disease status or response to medical products/agents.
• Endpoint: A precisely defined variable intended to reflect an outcome of interest, statistically analyzed to address a research question.
• Context of Use (COU): A statement fully describing how the biomarker is to be used and its purpose.
• Validation: Establishing that the performance of a test, tool, or instrument is acceptable for its intended purpose. Includes:
  • Construct Validation: Establishing logical relationships with other measures.
  • Content Validation: Establishing comprehensiveness relative to the concept of interest.
  • Analytical Validation: Establishing performance characteristics (sensitivity, specificity, accuracy, precision).
  • Clinical Validation: Establishing the ability to identify, measure, or predict the concept of interest.

Non-responsive studies include:

• Primary intent is therapeutic agent/device development.
• Primary intent is clinical safety, efficacy, effectiveness, or management of therapeutic agents/devices.
• Pre-clinical research using animal or in vitro models.
• Primary intent is diagnostic or risk assessment/biomarker development (not monitoring/endpoint).
• Applications lacking a "contexts of use" statement specifying unmet need and defining three or more diseases/conditions.
• Applications proposing to develop a device or app rather than using existing ones.
• Applications that do not include milestones.
• Applications that do not include diseases/conditions within participating NIH IC missions.

Encouragement to Contact NIH: Potential applicants are strongly encouraged to contact NIH Scientific/Research staff prior to preparing an application to discuss fit with NIH IC missions and seek prior approval for budgets exceeding $500,000 direct costs per year.

Expectations and Requirements for Resource and Data Sharing:

• All applications must include a Data Management and Sharing (DMS) Plan compliant with the NIH Policy for Data Management and Sharing.
• Data should be shared as soon as possible, no later than publication or end of award period.
• Awardees are expected to share data and/or biospecimens through broad-sharing repositories.

IC Interest Areas:

• National Institute of Neurological Disorders and Stroke (NINDS): Interested in applications developing assessments for neurological diseases/conditions across the lifespan, aligning with the NINDS 2021-2026 Strategic Plan. Research outside NINDS mission or traditionally supported by other NIH ICs will not be considered.
• National Cancer Institute (NCI): Interested in applications focused on cancer-specific digital monitoring biomarkers, COAs, and endpoints. Cancer types/subtypes can be defined as separate diseases if justified. NCI is particularly interested in:
  • Addressing unmet needs of high-risk, understudied, or underserved cancer populations.
  • Developing/validating digital biomarkers for cancer treatment-related symptoms, sequelae, or outcomes.
  • Developing/validating cancer-specific biomarkers using analyte data from electrochemical DHTs.
  • Using DHTs to monitor physiological status or clinical outcomes (physical function, nutrition, sleep, mobility).
  • Using DHT data to monitor treatment response and inform treatment selection/dosing.
• National Institute on Aging (NIA): Interested in applications focusing on age-related neurological disorders, such as Alzheimer's Disease (AD) and related dementias (ADRD). Aligns with NIA/NAPA AD+ADRD Research Implementation Milestone for Diagnosis, Assessment, and Disease Monitoring. Applications addressing AD and ADRD are strongly encouraged.

Section II. Award Information

Funding Instrument: Cooperative Agreement (substantial Federal scientific or programmatic involvement is expected).

Application Types Allowed:

• New
• Resubmission

Clinical Trial? Optional (accepting applications that either propose or do not propose clinical trials).

Funds Available and Anticipated Number of Awards: Contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget:

• Application budgets are not limited but must reflect actual project needs.

Award Project Period:

• UG3 phase: 1-2 years
• UH3 phase: 3-4 years
• Maximum project period: 5 years (combined UG3 and UH3 phases).

NIH grants policies as described in the NIH Grants Policy Statement will apply.

Section III. Eligibility Information

1. Eligible Applicants:

• Eligible Organizations:
  • Higher Education Institutions (Public/State Controlled, Private)
  • Nonprofits Other Than Institutions of Higher Education (with 501(c)(3) IRS Status, without 501(c)(3) IRS Status)
  • For-Profit Organizations (Small Businesses, Other Than Small Businesses)
  • Local Governments (State, County, City/Township, Special District)
  • Indian/Native American Tribal Governments (Federally Recognized, Other than Federally Recognized)
  • Federal Government (Eligible Agencies)
  • U.S. Territory or Possession
  • Other (Independent School Districts, Public Housing Authorities/Indian Housing Authorities, Native American Tribal Organizations, Faith-based/Community-based Organizations, Regional Organizations)
• Foreign Organizations: Not eligible to apply.
• Non-domestic (non-U.S.) components of U.S. Organizations: Not eligible to apply.
• Foreign components: Allowed (as defined in the NIH Grants Policy Statement).

Required Registrations (Applicant Organizations):

• System for Award Management (SAM): Must be active and renewed at least annually.
• NATO Commercial and Government Entity (NCAGE) Code: Required for foreign organizations registering in SAM.
• Unique Entity Identifier (UEI): Obtained via SAM.gov registration.
• eRA Commons: Must be in place by submission time. Requires at least one Signing Official (SO) and one Program Director/Principal Investigator (PD/PI) account.
• Grants.gov: Must have an active SAM registration.

Registrations can take 6 weeks or more. Start early. Failure to complete registrations is not a valid reason for late submission.

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

• Must have an eRA Commons account.
• If also the Signing Official, must have two distinct eRA Commons accounts.
• Account creation 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.

2. Cost Sharing:

• Not required.

3. Additional Information on Eligibility:

• Number of Applications: Applicant organizations may submit more than one application if scientifically distinct. Duplicate or highly overlapping applications will not be accepted under review simultaneously.

Section IV. Application and Submission Information

1. Requesting an Application Package:

• Access through ASSIST, Grants.gov Workspace, or an institutional system-to-system solution.

2. Content and Form of Application Submission:

• Follow instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where specified otherwise in this NOFO.
• Page Limitations: Adhere to all page limitations specified in the Application Guide and Table of Page Limits.

Instructions for Application Submission (Supplements to Application Guide):

• SF424(R&R) Cover: Follow Application Guide instructions.
• SF424(R&R) Project/Performance Site Locations: Follow Application Guide instructions.
• SF424(R&R) Other Project Information: Follow Application Guide instructions.
• Timeline and Proposed Milestones (required; 3 pages maximum):
  • Describe project decision points with quantitative metrics for go/no-go decisions.
  • Include clear deliverables and Go/No-Go milestones at the end of the UG3 phase and annual quantitative milestones for each year of UG3 and UH3.
  • Provide success criteria and justification for each milestone.
  • Quantitative milestones should include progress metrics (e.g., community engagement, enrollment) and performance metrics (e.g., data quality, analytical thresholds).
  • A Gantt chart for the timeline is strongly encouraged.
• Team Management plan (required; 2 pages maximum):
  • Describe workflow and collaboration among multidisciplinary teams (clinical scientists, disease experts, statisticians, regulatory experts, etc.).
  • Include letters of support.
  • Focus on project management across sites, PIs, co-Is, and consultants.
  • Consider: organizational structure, shared vision, resource sharing, credit assignment, knowledge transfer, coordination, communication, intra-team data sharing.
• Community Engagement plan (required; 2 pages maximum):
  • Include in an "Other Attachment" titled "Community Engagement Plan.pdf".
  • Describe community engagement strategies, input, and collaborative research.
  • Identify community partners (e.g., community advisory boards, organizations, families) and their roles.
  • Justify how partners and involvement level will enhance the project and its relevance.
  • Demonstrate feasibility (e.g., letters of support, formal roles).
  • Serving as a research participant or solely informing recruitment/retention is not sufficient collaboration.
• Intellectual Property (IP) Strategy (if applicable):
  • Describe IP landscape for software/algorithms if commercialization is intended.
  • Include letters of freedom to operate if using third-party DHT IP.
  • Disclose details of any filed patents.
  • Discuss future IP filing plans and IP management for multi-institution applications.
• Other Attachments:
  • SF424(R&R) Senior/Key Person Profile: Follow Application Guide instructions.
  • R&R Budget: Follow Application Guide instructions.
  • R&R Subaward Budget: Follow Application Guide instructions.
  • PHS 398 Cover Page Supplement: Follow Application Guide instructions.
  • PHS 398 Research Plan: Follow Application Guide instructions, with additional instructions:
    • Context of Use and Specific Aims:
      • Contexts of Use: Describe how DHT-derived remote assessments will be used as endpoints, the types of clinical trials needed, and how they complement/replace existing standards.
      • Specific Aims: Briefly describe aims for UG3 and UH3 phases, questions to be answered, and general approach.
    • Research Strategy:
      • Clinical Contexts and Unmet Needs: Describe trial types, unmet endpoint needs, improvements over existing assessments, current standards, and limitations to overcome.
      • Premise and Rationale for Proposed DHT Derived Biomarkers or COAs: Define diseases/conditions, similarities/differences in use, relationship to biological/physiological processes or symptoms. Include a table specifying biomarkers/COAs and their intended "concept of interest". Describe why measurements are expected to reflect clinically meaningful changes and how "meaningfulness" was/will be established. Address rigor of preliminary data/literature.
      • Approach and Statistical Analysis Plans: Describe study designs and statistical approaches for UG3 and UH3. Address:
        • Best DHT(s) to use and selection criteria.
        • How technical validity (analytical validation) will be established in real-world environments.
        • How established outcome assessments/biomarkers will demonstrate construct validity.
        • Control groups for UH3, use of normative reference data, and controlling for confounds.
        • How the minimum clinically important difference (MCID) will be quantified at the individual level.
        • How the study will assess improvement over existing measures.
      • Scientific Rigor: Emphasize rigor and transparency (see NIH guidance). Rationale must be based on robust data. Address potential bias, blinding, randomization, sample size, inclusion/exclusion criteria, handling missing data, appropriate controls, preplanned analyses, and quantitative techniques.
      • Resource Sharing Plan: Comply with Application Guide instructions.
      • Other Plan(s):
        • Data Management and Sharing Plan: Required for all applications generating scientific data. Address elements described in NOT-OD-21-014.
      • Appendix: Limited materials allowed. No publications or other material except blank questionnaires/surveys.
    • PHS Human Subjects and Clinical Trials Information: Follow Application Guide instructions. Include at least one human subjects study record if applicable.

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

• See Part 2. Section III.1 for registration requirements.

4. Submission Dates and Times:

• Refer to Part 1 for Key Dates.
• Applications are due by 5:00 PM local time of the applicant organization.
• Submission date is automatically extended to the next business day if it falls on a weekend or Federal holiday.
• Submit to Grants.gov. Track status in eRA Commons.
• Correct errors and submit changed/corrected applications by the due date and time. Late applications are subject to NIH Grants Policy Statement Section 2.3.9.2.
• Applicants are responsible for viewing their application in eRA Commons before the due date.

5. Intergovernmental Review (E.O. 12372):

• Not applicable.

6. Funding Restrictions:

• Awards are subject to the NIH Grants Policy Statement.
• Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1.

7. Other Submission Requirements and Information:

• Applications must be submitted electronically. Paper applications will not be accepted.
• Complete all required registrations before the application due date.
• For assistance, visit the How to Apply – Application Guide.
• Follow Dealing with System Issues guidance if system problems threaten timely submission.
• Important reminders:
  • Include PD/PI eRA Commons ID in the Credential field of the Senior/Key Person Profile form.
  • Ensure the unique entity identifier matches between SAM and eRA Commons.
• Webinar: A pre-application informational webinar will be held annually in December. Recordings will be posted at: https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research under News & Events. Registration details are on the NINDS Events page.
• Requests of $500,000 or more in direct costs: Contact a Scientific/Research Contact at least 6 weeks before submission.
• Mandatory Disclosure: Recipients must disclose violations of federal criminal law involving fraud, bribery, or gratuity violations affecting the federal award (2 CFR 200.113, NIH Grants Policy Statement Section 4.1.35). Send disclosures to the NIH Chief Grants Management Officer and the HHS Office of Inspector General.
• Post Submission Materials: Follow instructions in the policy.

Section V. Application Review Information

1. Criteria: Applications are evaluated for scientific and technical merit through NIH peer review.

• Overall Impact: Reviewers assess the likelihood of the project exerting a sustained, powerful influence on the research field(s).

• Review Criteria:

  • Factor 1: Importance of the Research
    • Significance: Importance in the context of scientific challenges, advancing knowledge, addressing gaps, solving problems, or creating advances. Rigor of scientific background and justification.
    • Innovation: Novel concepts, methods, or technologies, or novel uses of existing ones.
    • Specific to this NOFO: Likelihood of proposed DHT-derived biomarker(s)/COA(s) being used in future clinical trials; added value in reducing burden or improving trial efficiency; benefits outweighing implementation issues.
  • Factor 2: Rigor and Feasibility
    • Approach: Scientific quality, likelihood of reproducible findings (rigor), and ability to be done well within timeframes (feasibility).
      • Rigor: Potential for unbiased, reproducible data; rigor of experimental design and controls; sufficient sample size; quality of analysis/interpretation plans; plans to address biological variables (sex, age); rigor of intervention/manipulation (if applicable); justification of outcome variables; generalizability/relevance; appropriateness and diversity of sample; adequacy of human subject inclusion plans.
      • Feasibility: Soundness and achievability of the approach; plans to address challenges; balance of uncertainty vs. potential advances; adequacy and feasibility of human subject recruitment/retention plans; likelihood of achieving enrollment targets; feasibility of study timeline and milestones (for clinical trials).
    • Specific to this NOFO: Appropriateness of milestones with quantitative Go/No-Go criteria; clarity of milestones as indicators of feasibility and performance metrics; assessment of the Community Engagement plan (roles, resources, benefits, dissemination, feasibility); how experimental design tests the proposed Contexts of Use.
  • Factor 3: Expertise and Resources
    • Investigator(s): Demonstrated background, training, and expertise. Quality of leadership plan for MPI applications.
    • Environment: Appropriateness of institutional resources.

• Additional Review Criteria (considered but not scored):

  • Specific to this NOFO: Concerns with the Intellectual Property (IP) strategy that could be a barrier to translational success.
  • Protections for Human Subjects: Risk, protection adequacy, potential benefits, importance of knowledge, data and safety monitoring.
  • Vertebrate Animals: Justification, minimization of discomfort, euthanasia methods.
  • Biohazards: Potential hazards and proposed protections.
  • Resubmissions: Full application as presented.
  • Renewals/Revisions: Not Applicable.

• Additional Review Considerations (not scored):

  • Authentication of Key Biological and/or Chemical Resources: Plans for identifying and ensuring validity.
  • Budget and Period of Support: Justification and reasonableness.

2. Review and Selection Process:

• Applications are evaluated by Scientific Review Groups (SRGs) convened by the ICs.
• Applications receive a written critique.
• Applications may undergo a selection process where only the highest-scoring applications are discussed.
• Applications are assigned to the appropriate NIH Institute or Center.
• Funding decisions consider:
  • Scientific and technical merit.
  • Availability of funds.
  • Relevance to program priorities.
• "Just-in-time" information may be requested before an award.
• NIH reviews federal award history in SAM.gov to assess applicant risk.

3. Anticipated Announcement and Award Dates:

• Summary Statements (written critiques) will be available via eRA Commons.
• Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
• Disposition of applications information is in the NIH Grants Policy Statement Section 2.4.4.

Section VI. Award Administration Information

1. Award Notices:

• A Notice of Award (NoA) is the official authorizing document.
• Awards are subject to all provisions in effect during the award period, Department regulations, and applicable statutes.
• Recipients must comply with funding restrictions in Section IV.6.
• Pre-award costs are at the applicant's risk.
• ClinicalTrials.gov: Responsible parties must register and submit results for applicable clinical trials. NIH expects registration and results reporting for all trials.
• Institutional Review Board or Independent Ethics Committee Approval: Required. Recipients must provide NIH copies of major changes to ongoing protocols.
• Data and Safety Monitoring Requirements: Required for all NIH-conducted or supported human intervention studies (clinical trials).
• Investigational New Drug or Investigational Device Exemption Requirements: Must be performed under FDA IND or IDE if applicable.

2. Administrative and National Policy Requirements:

• 2 CFR Part 200: Uniform Administrative Requirements, Cost Principles, and Audit Requirements.
• NIH Grants Policy Statement: Applies to all awards.
• Nondiscrimination Laws: Recipients must comply and submit an Assurance of Compliance (HHS-690).
• Federal statutes and regulations: Including those in NIH Grants Policy Statement Section 4.
• Termination: NIH may terminate awards for noncompliance (2 CFR Part 200.340, NIH Grants Policy Statement Section 8.5.2).
• Health IT Standards: Recipients implementing, acquiring, or upgrading health IT must use standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if applicable.
• ONC Health IT Certification: Use certified technology if applicable for eligible clinicians/hospitals under HITECH Act.
• Cybersecurity: Recipients with ongoing access to HHS systems and PII/PHI must develop plans modeled after the NIST Cybersecurity framework.

Cooperative Agreement Terms and Conditions of Award:

• Substantial NIH programmatic involvement is anticipated. NIH supports and guides recipients in a partnership role, not assuming direction or a dominant role. Prime responsibility resides with recipients.

• PD(s)/PI(s) have primary responsibility for:

  • Defining objectives and approaches.
  • Planning, conducting, analyzing, interpreting, and publishing studies.
  • Developing rigorous milestones.
  • Pursuing patent protection.
  • Providing complete progress reports, including raw data upon request.
  • Participating in virtual progress meetings (1-2 times/year).
  • Communicating regulatory meeting dates/agendas and inviting NIH participation.
  • Communicating study reports, meeting minutes, and communications with FDA/authorities.
  • Providing regulatory and clinical documents for administrative review.
  • Verifying clinical study adherence to Good Clinical Practices (GCP) and IC-specific guidelines.

• NIH staff have substantial programmatic involvement:

  • Subject Matter Experts (SMEs) from NIH program staff will advise on project approvals and landscape of disease/condition.
  • Program Officer(s) assigned for scientific/programmatic stewardship and guidance.
  • Program Officer(s) will develop and negotiate final milestones with PD/PIs.
  • Program Officer(s) assess progress towards milestones and recommend funding release.
  • Program Officer(s) may require regulatory input and share results.
  • Program Officer(s) may consult with other NIH staff.
  • Continuation of funding recommendations are made by Program Officer(s), reviewed by Associate Division Director.
  • Funding decisions consider progress, milestones, programmatic priorities, budget, competitive landscape, and fund availability.
  • Future-year milestones may be renegotiated.
  • Funding may be discontinued if milestones are not met.
  • Milestone negotiation and finalization are collaborative.
  • Virtual meetings (1-2 times/year) for PD/PIs to provide updates.

• Areas of Joint Responsibility:

  • Milestone negotiation and finalization.
  • Virtual progress meetings.

• Dispute Resolution: A special dispute resolution procedure is available for disagreements on scientific or programmatic matters.

3. Data Management and Sharing:

• Recipients must adhere to the Data Management and Sharing requirements outlined in the NIH Grants Policy Statement and their approved DMS Plan.

4. Reporting:

• Research Performance Progress Report (RPPR) required annually.
• Financial statements as required.
• Final RPPR, invention statement, and expenditure data required for closeout.
• Performance is measured based on details and outcomes shared in the RPPR.

5. Evaluation:

• (No specific evaluation criteria detailed in this section).

Section VII. Agency Contacts

Inquiries: Inquiries concerning this funding opportunity are encouraged.

Application Submission Contacts:

• eRA Service Desk:
  • Online: https://www.era.nih.gov/need-help (preferred)
  • Phone: 301-402-7469 or 866-504-9552 (Toll Free)
• General Grants Information:
  • Email: [email protected] (preferred)
  • Phone: 301-480-7075
• Grants.gov Customer Support:
  • Phone: 800-518-4726
  • Email: [email protected]

Scientific/Research Contact(s):

• Carol Taylor-Burds, PhD (NINDS)
  • Phone: 301-496-1779
  • Email: [email protected]
• Dana L. Wolff-Hughes, Ph.D. (NCI)
  • Phone: 240-620-0673
  • Email: [email protected]
• Yuan Luo, Ph.D. (NIA)
  • Phone: 301-496-9350
  • Email: [email protected]

Peer Review Contact(s):

• Chief, Scientific Review Branch (NINDS)
  • Email: [email protected]

Financial/Grants Management Contact(s):

• Chief Grants Management Officer (NINDS)
  • Email: [email protected]
• Crystal Wolfrey (NCI)
  • Phone: 240-276-6277
  • Email: [email protected]
• Philip Smith (NIA)
  • Phone: 301-402-3465
  • Email: [email protected]

Section VIII. Other Information

• Recently issued trans-NIH policy notices may affect application submission. Refer to 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 2 CFR Part 200.

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