This NIH funding opportunity (PAR-25-170) supports rigorous development and validation of digital health technology (DHT)-derived biomarkers and clinical outcome assessments for remote patient monitoring and clinical trial endpoint development. Administered through a two-phase UG3/UH3 cooperative agreement structure, the program involves NCI, NINDS, and NIA, with co-funding from OBSSR.

Eligible applicants include academic and research institutions; partnerships with nonprofit patient advocacy organizations are required. Applications are due June 22, 2026. The program was updated in March 2025 to align with revised agency priorities.

PAR-25-170: Digital Health Technology Derived Biomarkers and Outcome Assessments for Remote Monitoring and Endpoint Development (UG3/UH3 - Clinical Trial Optional) 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. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and National Cancer Institute ( NCI ) National Institute on Aging ( NIA ) December 13, 2024 - Participation added ( NOT-AG-24-083 ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

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) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement 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 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 .

Funding Opportunity Number (FON) Companion Funding Opportunity See Part 2 Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) 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.

To increase standardization and improve clinical adoption, applicants must propose to develop and evaluate the DHT enabled biomarkers or COAs in three or more diseases or conditions. Applicants must also propose to conduct development studies that are informed by people with lived experience (PWLE) and patient advocacy organizations.

The first phase of this funding mechanism is to evaluate the technical performance of the proposed DHTs withPWLE input; the second phase is to support a prospective longitudinal clinical study in representative populations to validate the DHT.

Research outcomes should include demonstrating 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 that explores the fundamental structure and function of the brain and the nervous system; research to understand the causes and origins of pathological conditions of the nervous system with the goal of preventing these disorders; research on the natural course of neurological disorders; improved methods of disease prevention; new methods of diagnosis and treatment; drug development; development of neural devices; clinical trials; and research training in basic, translational and clinical neuroscience.

The Institute is the largest funder of basic neuroscience in the US and supports research on topics including but not limited to: development of the nervous system, including neurogenesis and progenitor cell biology, signal transduction in development and plasticity, and programmed cell death; synapse formation, function, and plasticity; learning and memory; channels, transporters, and pumps; circuit formation and modulation; behavioral and cognitive neuroscience; sensorimotor learning, integration and executive function; neuroendocrine systems; sleep and circadian rhythms; and sensory and motor systems.

In addition, the Institute supports basic, translational and clinical studies on a number of disorders of the nervous system including (but not limited to): stroke; traumatic injury to the brain, spinal cord and peripheral nervous system; neurodegenerative disorders; movement disorders; brain tumors; convulsive disorders; infectious disorders of the brain and nervous system; immune disorders of the brain and nervous system, including multiple sclerosis; disorders related to sleep; and pain.

Programmatic areas, which are primarily supported by the Division of Neuroscience, are also supported by the Division of Extramural Activities, the Division of Translational Research, the Division of Clinical Research, the Office of Training and Workforce Development, the Office of Programs to Enhance Neuroscience Workforce Development, and the Office of International Activities.

(2) To expand and improve the Small Business Innovation Research (SBIR) program; to increase private sector commercialization of innovations derived from Federal research and development; to increase small business participation in Federal research and development; and to foster and encourage participation of socially and economically disadvantaged small business concerns and women-owned small business concerns in technological innovation.

To utilize the Small Business Technology Transfer (STTR) program; to stimulate and foster scientific and technological innovation through cooperative research and development carried out between small business concerns and research institutions; to foster technology transfer between small business concerns and research institutions; to increase private sector commercialization of innovations derived from Federal research and development; and to foster and encourage participation of socially and economically disadvantaged small business concerns and women-owned small business concerns in technological innovation.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description There is a high unmet need for clinical endpoints that can be assessed remotely in clinical trials.

As defined in the FDA/NIH’s Biomarkers, EndpointS, and other Tools (BEST) resource, an endpoint is “a precisely defined variable intended to reflect an outcome of interest that is statistically analyzed to address a particular research question”. In clinical trials, endpoints may include one or more clinical outcome assessment and/or biomarkers.

Regulatory agencies, industry, and funding organizations recognize the potential of developing endpoints that can be deployed remotely for use in clinical trials to assess efficacy. Remote monitoring assessment tools may include wearable or home monitoring sensor-based digital health technologies (DHTs) or software-based applications that can be used from a web-based application such as a tablet, phone or computer.

Remote assessments can improve clinical research by reducing the burden on study participants and caregivers and can be more sensitive to clinically meaningful changes over time due to more frequent assessments that are less susceptible to the variability from differences in an individual’s state at the time of a single clinical visit.

However, successful development of meaningful endpoints requires carefully thought-out and rigorous studies in collaboration with study participants and caregivers (“people with lived experience”; PWLE) to help guide what is “meaningful” and feasible.

Although the use of validated digital endpoints is expected to revolutionize clinical trials, successful implementation and regulatory acceptance requires extensive fit-for-purpose validation and must be able to demonstrate that the endpoints reflect clinically meaningful changes in how participants feel, function, or survive.

Therefore, studies proposing to develop and validate assessments for future clinical trial endpoints need to understand the regulatory expectations to successfully design and conduct the studies needed to support the evidentiary requirements.

While acceptance of web-based applications and DHT derived endpoints by regulatory agencies will require final validation in clinical trials, there is substantial preliminary work that must be done for the initial development and proof of concept clinical validation.

Guidance from the Food and Drug Administration (FDA), and Centers for Medicare & Medicaid Services (CMS) among others, highlights several critical questions that need to be clearly addressed, justified, and supported by high quality data.

Many traditional clinical outcome assessments and biomarkers used for monitoring disease progression or response to an intervention are applicable to more than one disease or condition: they may share common cognitive, motor, or physiological processes, but may manifest and progress at different rates.

Developing and validating DHT derived assessments or biomarkers for remote monitoring is a resource intensive process requiring complex analyses of the high-dimensional datasets generated.

The goals of this NOFO are to 1) encourage collaboration across disease areas to pool expertise and resources, and 2) support research to generate the data needed for the development, analytical validation, and proof of concept clinical validation of DHT derived assessments and monitoring biomarkers to be used as future endpoints in clinical trials for three or more disease areas .

Research scope and special requirements and considerations: Partnerships with patient advocacy organizations and people with lived experience (PWLE) are required to inform study design, endpoint selection, and increase community uptake.

Three or more diseases/conditions are required to encourage standardization of remote monitoring assessment and endpoint development and to promote collaboration and pooled resources and successful translation.

Development and validation of the proposed remote assessments should fill an unmet need as primary or secondary endpoints in clinical trials, which may include, but is not limited to clinical trials for therapeutic development or rehabilitation research, comparative effectiveness research, and/or clinical trials for interventions for preventative medicine approaches.

As part of defining the contexts of use (COU), consideration should be given to the feasibility of integrating the remote assessments into clinical trials as primary or secondary endpoints. For the purposes of this NOFO , digital health technologies may include sensor based digital health technologies such as wearable devices, in home technologies, or web-based applications.

A community engagement plan is required that outlines how communities will be engaged throughout the research process. The plan should identify relevant invested parties as collaborators at a level of involvement that is meaningful and feasible for the community partner(s) and appropriate for the project to enhance the impact of the research.

No specific community engaged research approach is required but please see the National Academy of Medicine’s Advancing Health Equity and Systems Transformation through Community Engagement strategy for assessing meaningful community engagement as a reference and to identify core principles to follow (see Other Attachments section in Section IV).

A timeline, annual milestones and UG3/UH3 Transition that describe the project decision points with quantitative metrics for go/no-go decision making throughout the project timeline must be included (see Other Attachments section in Section IV).

At the UG3/UH3 Transition the applicant will be required to submit a research performance progress report (RPPR) that includes the list of completed milestones (developed in collaboration with the PI as part of the initial Notice of Award) to progress to the UH3 implementation phase.

These UH3 transition requests will undergo administrative review by NIH staff to determine whether the study will be awarded the implementation phase (UH3). Transition decisions will be based on achievement of study milestones, readiness to conduct the UH3 study, feasibility of completing the UH3 study, availability of funds, and program priorities.

Appropriate activities for each phase of the UG3/UH3 mechanism may include, but are not limited to: First Phase (UG3; 1-2 years): Device selection and analytical validation pilot studies to optimize the algorithms to measure the concept(s) of interest against gold standards in the target patient populations which may include construct and/or content validation.

May include head-to-head comparisons of different DHTs to select the best performing or evaluate the generalizability across devices in preparation for use in the second (UH3) phase. Evaluate factors that may interfere with the precision and accuracy of the data and measurement(s) made from the DHTs in real world environments.

Optimize and finalize protocols to ensure standardization across the sites and target populations; take into consideration missing data, amount of wear/use time needed for planned analyses in the prospective longitudinal clinical validation study (UH3 phase) Establish the final statistical analysis and data management plans for the UH3 phase.

Develop user-informed consent and training materials for the UH3 phase with input from individuals with lived experience (investigators are highly encouraged to review the Informed Consent for Research Using Digital Health Technologies: Points to Consider & Sample Language document from NIH: https://osp. od. nih.

gov/wp-content/uploads/2024/05/DigitalHealthResource_Final. pdf ). 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 UH3 phase validation study.

Obtain input from relevant regulatory agencies such as through Critical Path Innovation meetings (CPIM) and/or consultation with the FDA’s Drug Development Tools qualification programs ( https://www. fda. gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs ) and/or meetings with the Centers for Medicare & Medicaid Services (CMS) (Coverage with Evidence Development: https://www.

cms. gov/medicare-coverage-database/view/medicare-coverage-document. aspx?

mcdid=38 ). Second Phase (UH3; 3-4 years but no more than 5 years for both the UG3 and UH3 phases combined): 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. Obtain regulatory input such as through a Critical Path Innovation Meetings (CPIM) and/or submission of a letter of intent to one of the FDA’s Drug Development Tools qualification programs.

Definitions used in this NOFO: Disease/condition: A disorder of structure or function, which may have a known cause and a distinctive group of symptoms, signs, or anatomical changes. How a disease or condition is defined may evolve along with the biological understanding of the etiology or symptomatology.

For purposes of this NOFO, applicants should reference the criteria used to define the disease/condition which may include definitions from clinical practice guidelines or consensus papers, or similar standardized definitions. Digital Health Technologies and sensor-based digital health technology (DHT) are a system that uses computing platforms, connectivity, software, and/or sensors for healthcare and related uses.

For the purpose of this NOFO, DHTs may refer to wearable sensors, mobile/app based cognitive or functional assessments, and in-home monitoring technologies. Remote assessment: Collection of data from a participant’s location that is distant from the investigator or trial personnel.

Concept of interest (COI): the aspect of an individual’s clinical, biological, physical or functional state, or experience that the assessment is intended to indicate or reflect. 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 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. Endpoint: A precisely defined variable intended to reflect an outcome of interest that is statistically analyzed to address a particular research question.

A precise definition of an endpoint typically specifies the type of assessments made, the timing of those assessments, the assessment tools used, and possibly other details, as applicable, such as how multiple assessments within an individual are to be combined (BEST Glossary: https://www. ncbi. nlm.

nih. gov/books/NBK338448/#IX-E ). 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.

Validation: A process to establish that the performance of a test, tool, or instrument is acceptable for its intended purpose.

This may include: Construct Validation: A process to establish, using quantitative methods, the extent to which the relationships among items, domains, and concepts of a clinical outcome assessment conform to a priori hypotheses concerning logical relationships that should exist with other measures or characteristics of patients and patient groups.

Content Validation: A process to establish from qualitative research the extent to which the clinical outcome assessment instrument measures the concept of interest including evidence that the items and domains of an instrument are appropriate and comprehensive relative to its intended measurement concept, population, and use.

Analytical Validation: A process to establish that the performance characteristics of a test, tool, or instrument are acceptable in terms of its sensitivity, specificity, accuracy, precision, and other relevant performance characteristics using a specified technical protocol. This is validation of the test’s, tool’s, or instrument’s technical performance, but is not validation of the item’s usefulness.

Clinical Validation : A process to establish that the test, tool, or instrument acceptably identifies, measures, or predicts the concept of interest.

Non-responsive studies include: clinical trials or clinical research where the primary intent is to develop therapeutic agents or devices, clinical trials or clinical research to evaluate a therapeutic agent or device’s clinical safety, efficacy, effectiveness, and/or clinical management, pre-clinical research using animal models or in vitro models, applications where the primary intent is to develop diagnostic or risk assessments or biomarkers rather than for monitoring/endpoint development.

applications that do not include a statement titled “contexts of use” that specifies how the proposed endpoints will fill an unmet need for the diseases/conditions specified, and clearly defines the three or more diseases/conditions to be included, applications that are proposing to develop a device or app rather than using existing devices/platforms, applications that do not include milestones, applications that do not include diseases/conditions within the participating NIH IC missions.

Non-responsive applications will be administratively withdrawn without review. Potential applicants are strongly encouraged to contact NIH Scientific/Research staff and participating NIH Institutes/Centers prior to preparing an application to discuss whether their application fits the mission of a particular NIH IC and seek prior approval for applications expecting to exceed the $500,000 direct costs per year budget cap.

See also under Section IV. 7 below ("Other Submission Requirements and Information"). Expectations and Requirements for Resource and Data Sharing: The NIH Policy for Data Management and Sharing (Policy) expects researchers to maximize the sharing of scientific data and data be accessible as soon as possible and no later than the time of an associated publication or the end of the award period, whichever comes first.

NIH requires all applications submitted in response to this NOFO to include a Data Management and Sharing Plan (DMS Plan). The DMS Plan is expected to address the Elements as described in Supplemental Information to the NIH Policy for Data Management and Sharing: Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014). The DMS Plan will be reviewed and approved by NIH Program Staff prior to award.

Awardees will be required to comply with their approved Plan and any approved updates. Awardees are expected to share data and/or biospecimens through broad-sharing data and/or biospecimen repositories. For applications that aim to analyze existing data, DMS plans should describe where and how other researchers can access that data to enable reproducibility and reuse.

National Institute of Neurological Disease and Stroke (NINDS) National Cancer Institute (NCI) NCI is interested in applications aligned with the NCI mission and scientific priorities and focused on the development and validation of cancer-specific digital monitoring biomarkers, clinical outcome assessments, and endpoints.

As cancer is a group of diseases, applicants may define each cancer type or subtype (including molecular subtypes) as separate diseases if scientifically justified.

NCI is particularly interested in applications that: Address unmet needs of high-risk, understudied, and/or underserved cancer populations including but not limited to individuals with early-onset cancers, rare cancers, pediatric cancer survivors, older cancer patients with comorbities, and rural patient communities, Develop and validate digital biomarkers to monitor cancer treatment related symptoms, sequelae, and/or outcomes (e.g., pain, cognitive impairment, adverse events, late effects toxicity), Develop and validate cancer-specific biomarkers using analyte data derived from electrochemical DHTs, Use DHTs to monitor physiological status and/or clinical outcomes associated with physical function, nutritional or dietary status, aerobic capacity, body composition, sleep/circadian disruption, and/or mobility, and Use DHT-measured physiological and analyte data to monitor treatment response and inform treatment selection, optimized dosing, and adaptive designs.

National Institute of Aging (NIA) NIA is interested in applications that focus on development, verification and validation of digital biomarkers and digital clinical outcome assessments in age-related neurological disorders, such as Alzheimer’s Disease (AD) and related dementias (ADRD). AD/ADRD are a spectrum of conditions that cause a decline in cognition, function, and behavior.

In addition to AD, examples of ADRD are Lewy body dementia (LBD), frontotemporal disorders (FTD), limbic-predominant age-related TDP-43 encephalopathy (LATE), Vascular contributions to cognitive impairment and dementia (VCID) as well as mixed dementias.

Through this NOFO, NIA supports research based on systematic collection, scientifically sound analysis, and interpretation of clinically meaningful health information to improve age-related outcomes, decrease health disparities and improve care delivery of older adults.

This NOFO is aligned with NIA/NAPA AD+ADRD Research Implementation Milestone for Diagnosis, Assessment, and Disease Monitoring , as well as joining the efforts to promote health for all by developing remote assessments that can reduce the barriers to participate in clinical trials. NIA welcomes applications aligned with NIA’s strategic mission . Applications addressing topics related to AD and ADRD are strongly encouraged.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for this NOFO. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Optional: Accepting applications that either propose or do not propose clinical trial(s). Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The UG3 phase may be 1-2 years, and the UH3 phase may be 3-4 years, with the maximum project period being no more than 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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 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. Applicant organizations must complete and maintain the following registrations as described in the How to Apply-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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications .

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.

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 How to Apply- Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply-Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply-Application Guide must be followed.

Timeline and Proposed Milestones (required; 3 pages maximum): Milestones should describe project decision points with quantitative metrics for go/no-go decision making throughout the funding period. Clear deliverables with corresponding Go/No-Go milestones should