National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Cancer Institute (NCI)
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)
See Part 2 Section III. 3. Additional Information on Eligibility.
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.
(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.
Letters of intent are requested, but not required, 30 days before the application due date.
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 |
February 21, 2025 | February 21, 2025 | Not Applicable | July 2025 | October 2025 | December 2025 |
June 20, 2025 | June 20, 2025 | Not Applicable | November 2025 | January 2026 | April 2026 |
February 20, 2026 | February 20, 2026 | Not Applicable | July 2026 | October 2026 | December 2026 |
June 22, 2026 | June 22, 2026 | Not Applicable | November 2026 | January 2027 | April 2027 |
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.
Not Applicable
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.
Background:
There is a high unmet need for clinical endpoints that can be assessed remotely in clinical trials. As defined in the FDA/NIHs 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 individuals 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:
Appropriate activities for each phase of the UG3/UH3 mechanism may include, but are not limited to:
First Phase (UG3; 1-2 years):
Second Phase (UH3; 3-4 years but no more than 5 years for both the UG3 and UH3 phases combined):
Definitions used in this NOFO:
Non-responsive studies include:
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.
IC Interest Areas:
National Institute of Neurological Disease and Stroke (NINDS)
NINDS is interested in applications that propose to develop assessments that meet an unmet need for neurological diseases and conditions across the lifespan. NINDS recognizes that DHT derived measurements needed for use in pediatric or elderly populations may be substantially different than adult populations and require distinct efforts. This NOFO is aligned with the NINDS 2021-2026 Strategic Plans priority areas of supporting the development and validation of biomarkers and outcome measures, as well as aiding in the efforts to promote health equity by supporting representative validation efforts and by developing remote assessments that can reduce the barriers to participate in clinical trials. Research activities outside of the NINDS mission or traditionally supported by another NIH Institute or Center that is not signed onto this NOFO will not be considered.
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:
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 Alzheimers 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 equity by developing remote assessments that can reduce the barriers to participate in clinical trials. NIA welcomes applications aligned with NIAs 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.
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.
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).
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Government
Other
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
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.
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.
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:
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.
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.
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:
The letter of intent should be sent to:
Carol Taylor-Burds, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: [email protected]
All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.
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.
All instructions in the How to Apply-Application Guide must be followed.
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 be included at the end of the UG3 phase and annual quantitative milestones are required for each year of the UG3 and UH3 phases as indicators of a project's continued progress or emergent difficulties. Milestones will be used to monitor project progress as part of the evaluation for continued funding by the Program Official and Project Scientists.
For each milestone, provide a brief description of the success criteria and justification for those criteria.
A Gannt chart for the timeline of attaching each milestone is strongly encouraged.
Team Management plan (required; 2 pages maximum)
All applicants must include a team management plan that describes the workflow of the team/key personnel. Applicants are strongly encouraged to form multidisciplinary teams that consist of clinical scientists, disease/biology matter expertise, statisticians, particularly those with clinical trial design expertise, regulatory expertise, and other academic/industry experts relevant to the modalities used in the application. Describe how the team will work together (e.g., data generation, reporting of data and integrated review across teams with various disciplines, decision-making, etc.) over the course of the project and include letters of support (below). This section should be complementary to the Multiple PD/PI Leadership Plan leadership plan by focusing on how the project will be managed across sites, PIs, co-Is and consultants. Effective project management is a critical component of achieving the program goals, especially as the team size increases. Elements to consider include:
Community engagement plan (required; 2 pages maximum):
Community engagement plan: In an Other Attachment entitled Community Engagement Plan.pdf, all applicants must include a summary that describes how community engagement strategies, community input, and community-engaged research will be incorporated throughout the study. The attachment should describe the community partners (e.g, who they consist of – community advisory boards, community organization, families from diverse linguistic and cultural backgrounds), their role, and how they will be collaboratively engaged in the research project (e.g., activities, frequency and duration of involvement). The community engagement plan should justify how the planned partners and level of involvement will enhance the research project and relevance of the project to the communities the research is meant to impact. The plan also should demonstrate the feasibility of engaging the community partners in the research at the planned level of involvement. Demonstration of feasibility should include (but is not limited to) letters of support and/or formal roles on the application (e.g., co-investigator, consultant).Serving as a research participant is not considered a collaboration, nor is solely informing recruitment and retention strategies.
Intellectual property (IP) Strategy
If applicable, applications should include an Intellectual property (IP) strategy. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials.
Applicants should describe the IP landscape surrounding any software development or analysis algorithms if commercialization is intended and any known constraints that could impede development and how they will be addressed. If the applicant proposes using a DHT whose IP is not owned by the applicant's institution, the applicant should include a letter addressing their freedom to operate (see letter of support) from any entities owning the IP, and indicating there will not be any limitations imposed on the studies or the product which would impede achieving the goals of the funding program.
If patents pertinent to the DHT derived biomarker or COA being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable.
Applicants should discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe 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. Applicants should clarify how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved.
Other Attachments:
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply-Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:
Context of Use and Specific Aims
Contexts of Use: briefly describe the contexts of use as to how the proposed DHT derived remote assessments (biomarkers and/or COAs) will be used as primary or secondary endpoints, what type(s) of clinical trials they are currently most needed for, and how they would be used to complement or replace existing standards.
Specific Aims; Briefly describe the project aims for both the UG3 and UH3 phases, including the questions to be answered and general approach taken.
Research Strategy
The Research Strategy Section should include the following sections and address (but is not limited to) the following topics:
Clinical Contexts and Unmet Needs:
Premise and Rationale for the Proposed DHT Derived Biomarkers or COAs:
Approach and Statistical Analysis Plans:
Describe the overall study designs and statistical approaches for the UG3 and UH3 phases and describe how the studies are designed to establish:
Scientific Rigor:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.
Other Plan(s):
All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:
Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.
When involving human subjects research, clinical research, and/or NIH-definedclinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- 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 How to Apply-Application Guide must be followed.
All instructions in the How to Apply-Application Guide must be followed.
See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIHs 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 How to Apply- Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.
Applications must be submitted electronically following the instructions described in the How to Apply-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 organizations profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply-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.
Webinar
In order to learn more about this NOFO and to have the opportunity to ask questions, a pre-application informational webinar will be held once a year in December, and the recording will be posted online at: https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research under the News & Events section.
Information on how to register for the webinar is posted on the NINDS Events page: https://www.ninds.nih.gov/news-events/events?page=1 under PAR Webinar: Digital Health Technology Derived Biomarkers and Outcome Assessments for Remote Monitoring and Endpoint Development (UG3/UH3 - Clinical Trial Optional)
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the How to Apply-Application Guide.
Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.
Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].
Applicants are required to follow the instructions for post-submission materials, as described in the policy
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.
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). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.
Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score.
Significance
Innovation
Specific to this NOFO:
Approach
Rigor:
Feasibility:
Specific to this NOFO;
Investigator(s)
Environment
.
As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.
Specific to this NOFO:
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, 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, 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.
When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals 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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.
Biohazards
When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.
Resubmissions
As applicable, evaluate the full application as now presented.
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.
Evaluate whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the ICs which applications are assigned in accordance with NIH peer review policies and practices, 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.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.
Prior to making an award, NIH reviews an applicants federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicants integrity, business ethics, and performance record of managing Federal awards per 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.
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.
A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipients business official.
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.
Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk. For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.
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).
The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:
All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.
Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. NIH may terminate awards under certain circumstances. See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.
Successful recipients under this NOFO agree that:
Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity. Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.
Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.
Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.
Successful recipients under this NOFO agree that:
When recipients, subrecipients, or third-party entities have:
1) ongoing and consistent access to HHS owned or operated information or operational technology systems; and
2) receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.
Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.
Consistent with the 2023 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.
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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.
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 Section 8.6 Closeout. 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 2 CFR Part 200.301.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Carol Taylor-Burds, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: [email protected]
Dana L. Wolff-Hughes, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-620-0673
Email: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]
Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS))
Email: [email protected]
Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email:[email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.