Part 1. Overview Information

Key Dates

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

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

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

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

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

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

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



Table of Contents
Part 1. Overview Information
Key Dates
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

Background

Advances in technology and data analytics have brought us closer to the future envisioned by the 2017-2027 NLM Strategic Plan in which “personal data collection becomes a foundation of self-knowledge and personal health management.” Individuals are becoming increasingly comfortable using mobile apps and wearables to help them track and monitor aspects of their health in real-time, including logging what they eat, measuring their heart rate, and recording how much they sleep. Improvements in the interoperability of electronic health records (EHRs) now enable a broader range of an individual’s care and health history to be integrated and analyzed together. Advances in artificial intelligence (AI) and machine learning (ML) have made it possible for researchers and healthcare providers to analyze large volumes of personal health data in real-time to gain a more comprehensive understanding of an individual’s health status and make meaningful predictions of health outcomes through the assessment of patterns, trends, and potential risks. By linking health data with other data sources, such as geospatial data, community-level data, health-related social needs, and social and structural determinants of health data, models can account for the significant role that social and environmental factors play in one’s health.

Personal health informatics tools, systems, and platforms leveraging AI/ML have the potential to provide individuals with actionable insights, tailored to their specific health risks and needs and automatically updated based on their personal health data streams and preferences. Predictions, forecasts, analyses, or other personalized outputs can be considered actionable insights when they are generated by scientifically validated models and presented in an understandable way that empower individuals to act on and respond to trends and features of their personal data. Informatics tools, systems, and platforms can be designed to make personalized recommendations for improving health, help people explore the potential future impact of different health choices, interpret and explain the results of predictive models, connect with virtual personalized health coaching or interventions, or even facilitate peer accountability through integration with social support networks.

Providing meaningful and actionable insights through personal health informatics still faces many technical challenges that require innovation to overcome. Personal health data may contain errors, omissions, or inconsistencies that can impact the accuracy and reliability of predictive models. Personal health data is often collected and stored in disparate systems that may not be compatible or interoperable. This can make it difficult to aggregate and analyze data from needed sources, limiting the accuracy and completeness of health risk estimates and personalized recommendations. Software that collects, aggregates, and analyzes personal health data must ensure appropriate safeguards are in place to protect individual privacy and confidentiality. To be trustworthy, tools, platforms, and systems leveraging AI/ML must be valid and reliable, safe, secure and resilient, accountable and transparent, explainable and interpretable, privacy enhanced, and fair with any potential biases identified and mitigated. Careful attention must be paid to ensure that previously validated predictive models can generalize their performance when applied in new settings, at different times, with updated data standards, or with different populations, for example.

Personal Health Informatics tools, systems, and platforms need to be designed for the end user to ensure effectiveness and accessibility. Additional research is needed to understand how to best present the insights generated by AI/ML to ensure they are understandable and interpretable by individuals. To be informed when evaluating the outputs of AI/ML, individuals may need to consider difficult to communicate concepts like uncertainty and risk, such as the uncertainty of a prediction or the change a certain behavior may have on their relative risk of developing a disease. Innovative approaches are needed to ensure the technology presenting AI/ML generated insights are accessible to a wide range of individuals, whose health literacy, language skills, technical sophistication, education levels, and cultural backgrounds and so forth vary. To advance the science of personal health informatics and effectively presenting AI/ML generated insights, researchers must engage end users and communities as research partners throughout the entire research process, which can be accomplished by using mixed methods, for example, along the collaborative design spectrum, from usability testing to co-design.

Specific Objectives and Scope of this NOFO

This NOFO invites research grant applications that will advance the development of innovative informatics and data science approaches that can help individuals understand and improve their health through actionable insights. For the purposes of this NOFO, the term individual refers to a person who intends to understand their health primarily for personal needs and may also include family members or friends consented to access an individual’s health care information in certain circumstances. Actionable insights are the predictions, forecasts, analyses, or other personalized outputs generated by scientifically validated models and presented in an understandable way that empower individuals to act on and respond to trends and features of their personal data. The NLM and other participating institutes seeks applications that further the science of providing meaningful and actionable insights to individuals through innovative personal health data collection, integration, analysis, and personalized assessments and interpretation. Applications seeking to advance the understanding of how informatics tools, platforms, or systems can best present the results, interpretation, and limitations of personalized assessments for the benefit of individuals are encouraged. Research seeking and studying innovative ways to combine and integrate technology (e.g. smartphones, wearable sensors, internet platforms, EHRs, AI/ML, predictive models) with biological, social, clinical, and behavioral knowledge to advance the performance of personalized assessments are encouraged.

Applications must clearly state a research question or questions to be answered using novel informatics and data science approaches. In the pursuit of these answers, applicants may find it suitable to develop, adapt, and study a range of personal health informatics tools, platforms, or systems for a variety of user needs. These may be condition/disease specific or provide a more holistic view of an individual’s health. Applicants must base their proposed work on an informed profile of the individuals who are the intended end users and available data. Applicants are encouraged to consider innovative ways to incorporate multiple data sources to help provide a portrait of an individual’s health, including consideration of the context in which it occurs, and impact of their actions. The work should be developed through interaction with the intended end users and are encouraged to follow principles of community engagement. If the approach focuses on a single disease, health condition, or narrow user group, applicants should provide assurance that their approach can be generalizable to other use cases and/or populations. Generally, NLM will not support full stack application development to meet the needs of a single niche group, unless the proposed method and group is uniquely suited to answer a critical research question.

Applicants should plan to undertake one or more studies to test the feasibility of their ideas using real-world data and/or acceptability of developed research products with the intended user group. The study should be designed to provide evidence of the degree of success of the innovative approach and/or needed next steps with the goal of informing the design of generalizable, reusable, and scalable personal health informatics tools, systems, and platforms.

Awardees are expected to share the results of their work through publication, and through open-source mechanisms for data or resource sharing. Awardees are expected to share results of their work with the communities and individuals who participate in the study and should consult with these groups to ensure the dissemination plan is meaningful and relevant. These materials should be created with readability and health literacy principles in mind. Applications should include a clearly described dissemination plan to ensure that software and data created through the work are readily usable and extensible, where applicable.

Specific areas of interest include, but are not limited to:

• How can AI/ML techniques extract and interpret patterns from an individual’s health data to provide meaningful and accurate insights, and how can these insights be communicated and used by individuals to improve health outcomes?
• How can data science approaches be used to develop personalized, informatics-based interventions for individuals based on their personal health data? How can these approaches be scaled to provide accurate insights across different populations and account for potential bias and health inequities?
• How can data science be used to integrate personal health data from multiple sources, such as EHRs, wearable devices, environmental sensors, geospatial data, community-level data, and social media, to provide individuals with a comprehensive and accurate view of their health?
• What data processing and analysis techniques are best suited for accurately generating actionable insights and risk assessments from personal health informatics data, which may be incomplete or contain errors?
• What are the most effective design features of individual-facing personal health informatics tools that promote engagement and positive health changes? How can technology be used to ensure these features are accessible and user-friendly for diverse groups, e.g. those with varied health and technology literacy levels, physical abilities, etc?
• How can emerging technologies, such as large language models, decision aids, and interactive visualization tools, be incorporated into personal health informatics tools to improve an individual’s understanding of the risks and recommendations and their associated limitations and accuracies generated by predictive models?  

Research Interests for the National Institute of Mental Health (NIMH):

NIMH encourages research that addresses institute priorities and is aligned with these recommended areas for domestic, global, and AIDS-related mental health research.

Note. Applicants are strongly encouraged to reach out to the NIMH scientific contact listed below regarding NIMH-specific data sharing and common data element policies (see NOT-MH-23-100, NOT-MH-20-067, NOT-MH-23-105) and clinical research guidelines (see NOT-MH-19-027).

Key characteristics of personal health informatics research that applicants may consider including in their applications (where applicable) include but are not limited to:

• Understanding of contextual factors that can influence the use of an individual-facing technology in various settings under investigation.
• Incorporation and justification of the use of theories, models, and/or frameworks that are relevant to community engagement, to inform study hypotheses, measures, tool development and design, and outcomes.
• Consideration of the extant literature on barriers to and facilitators of the use of health information technologies by individuals of diverse groups to improve health.
• Support of interoperability and data standards to improve data integration, interoperability, and exchange with other relevant systems or devices.
• Attention to issues of dissemination, generalizability, and scalability with the goal to bring the benefits of the proposed research findings and research products to more people on a lasting basis.
• Formation of transdisciplinary teams of researchers and stakeholders, given the range of expertise that may be needed for conducting personal health informatics research through community and end user engagement (e.g., bioinformatics, implementation scientists).

Applications Not Responsive to this NOFO:

The following will be considered non-responsive for this announcement and will not be reviewed:

• Projects seeking to develop predictive models that do not generate insights for individuals, e.g., a project that will develop a model to help administrators allocate resources across a healthcare organization, a project that will explore if a condition can be reliably diagnosed from a particular type of medical image, whose outputs will not be appropriate to share with individuals.
• Projects seeking support for tool or resource development that do not seek to answer research questions and advance the science of personal health informatics.
• Applications that provide health assessments that are not empirically based.
• Applications that do not propose to develop research products that are open source and will be freely available to biomedical and behavioral researchers and educators.

Where appropriate, it is strongly encouraged that applicants seek consultation from the Food and Drug Administration for guidance related to regulatory approval/certification of digital health interventions that are being tested. Under this NOFO, NLM and other participating institutes will support applications involving small, early-stage to Phase I clinical trials that are part of the evaluation component of the proposed research project. Applicants whose applications include a clinical trial are strongly encouraged to contact the scientific contacts listed in this NOFO for guidance in advance of applying to ensure that their proposed project follows NIH clinical trials policies (https://grants.nih.gov/policy/clinical-trials.htm) and is consistent with the types of clinical trial applications that NLM supports.

Applicants may propose new tools or extensions to the capabilities of existing open-source tools such as personal health record systems, by adding new features or extending capabilities of the tool to provide actionable insight. In either case, scientific innovation and the research question to be addressed is key. Applicants are encouraged to take advantage of freely available public information resources available from NLM and others, such as MedlinePlus, Genetics Home Reference, PUBMED Central, MetaMap.

Potential applicants are strongly encouraged to discuss their proposed project with one of the Scientific/Research Contact listed in Section VII for advice about the application process and suitability of the project for support by NLM and other participating institutes.

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Applicant Organizations

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

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

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Not Applicable

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy  

The objective of this Notice of Funding Opportunity (NOFO) is to advance the development of novel informatics and data science approaches that can help individuals understand and improve their overall health through actionable insights. Applications should involve end user engagement and real-world evaluation to inform the design of generalizable, reusable, and scalable personal health informatics tool. Multidisciplinary teams are encouraged and expected. 

The research strategy must: 

Significance

• Identify research question(s) to be addressed in the application, explain how answering these questions will drive scientific advancement in the field of personal health informatics with the goal of informing the design of generalizable, reusable, and scalable personal health informatics tools, systems, and platforms for the benefit of individuals in understanding and improving their health. The approach must use novel informatics and data science approaches and must be based on an informed profile of the intended end users and available data.
• Address the degree to which the proposed findings and products are scalable and could be disseminated into practice, given typically available resources (e.g., cost of a particular wearable device, user time, data quality), typical modes of engagement, and typical use patterns.
• Detail how the proposed research will generate data that will lead to a firm conclusion about the approach and provide information degree of success and/or needed next steps.
• Include a proposed impact statement should the project ultimately be successful.

Investigator(s)

• Describe plans to involve collaborations and/or input from engaging communities and individuals in a manner that informs the research (e.g., to help ensure the approaches are acceptable, feasible, and scalable) and helps to ensure the results will have utility for end users.

Innovation

• Explain how the proposed novel informatics and data science approaches can further the science of personal health informatics by providing meaningful and actionable insights to individuals through innovative personal health data collection, integration, analysis, and personalized risk assessments and interpretation.
• Highlight how innovative research strategies and design/analytic elements are incorporated, as appropriate, to enhance the study's potential for providing meaningful and actionable insights to individuals.
• Highlight how the application will leverage mobile health, health information technology, or other health related data (e.g. smartphones, wearable sensors, internet platforms, EHRs, geospatial data, community-level data, health-related social needs and social and structural determinants of health data) with biological, social, clinical, and behavioral knowledge to advance the performance of personalized assessments.

Approach

• Identify the end user whose needs are addressed by the study and provide a rationale for this population focus and description of the use case.
• Detail the rationale and empirical basis for the novel informatics or data science approach in terms of the intended target population; the availability and quality of informative and suitable personal health data; and the scientific validity, accuracy, and reliability of supporting models, algorithms, and methodology.
• Identify limitations or potential sources of bias of the datasets, algorithms, and applications to be used and provide mitigation strategies to avoid their amplification or perpetuation.
• Clearly describe how the proposed novel informatics or data science approach will be evaluated (e.g., in terms of accuracy, reliability, effectiveness, usability, security, privacy, and ethics.)
• Include plans for one or more studies with the intended user group and/or using real-world data and how this study will establish feasibility and acceptability.
• Include a plan for dissemination of research findings and products to 1) the scientific community and 2) the individuals and communities to be engaged in the research.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

Applicants are expected to include a general plan for timely dissemination and sharing resources, e.g., code, widely, as appropriate, and consistent with achieving the goals of the program in concert with policies of the NIH, NLM, and other participating institutes. A software dissemination plan, with appropriate timelines, is expected to be included to meet the goals of this initiative.

Applicants are expected to include a general plan for timely dissemination and sharing of data and resources, e.g., code, widely, as appropriate, and consistent with achieving the goals of the program in concert with policies of the NIH, NLM, and other participating institutes. A software dissemination plan, with appropriate timelines, is expected to be included to meet the goals of this initiative.

A major goal of this NOFO is to advance the development of novel informatics and data science approaches that can help individuals understand and improve their overall health through actionable insights. Applicants should therefore include detailed plans for open dissemination of methods, software, and tools to scientific and healthcare communities such that they are readily usable and extensible, where applicable. These should be made freely available to biomedical researchers and educators. There is no prescribed license for software produced by applications responding to this announcement, but any software license selected by applicants should allow for unrestricted redistribution and modification of software.

There is no prescribed license for software produced by applications responding to this announcement, but any software license selected by applicants should allow for unrestricted redistribution and modification of software.

Methods, tools, and software should be well documented and where applicable made available via version-controlled public repositories.

Where applicable, applicants should describe solutions for portable implementations to cloud and federated computing environments.

Solutions that enhance reproducibility when used by the community should be emphasized. These include:

• Any developed software should be freely available to biomedical researchers, curators, and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
• The terms of software availability should include the ability of outside researchers to modify the source code and to share modifications with other colleagues as well as with the investigators. The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
• To preserve utility to the community, the software should be transferable such that another individual or team can continue development if the original investigators are unwilling or unable to do so.

Applicants are encouraged to consider these additional best practices for sharing research software and source code.

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

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

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

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The objective of this Notice of Funding Opportunity (NOFO) is to advance the development of novel informatics and data science approaches that can help individuals understand and improve their overall health through actionable insights.  

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

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

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

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NLM, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 

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 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:

• Scientific and technical merit of the proposed project as determined by scientific peer review
• Application innovation and advancement of methods/approaches
• Availability of funds
• Relevance of the proposed project to program priorities

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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

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

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

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

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

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (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: support@grants.gov

Allison Dennis, PhD
National Library of Medicine (NLM)
Telephone: 301-827-9721
Email: allison.dennis@nih.gov

Lori A.J. Scott-Sheldon, Ph.D.
Division of AIDS Research
National Institute of Mental Health
Telephone: 301-792-2309
Email: lori.scott-sheldon@nih.gov

Zoe Huang, MD
National Library of Medicine (NLM)
Telephone: 301-496-4253
Email: huangz@mail.nlm.nih.gov

Andrea Culhane
National Library of Medicine (NLM)
Phone: 301-402-0069
E-mail: andrea.culhane@nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email:siscor@mail.nih.gov

Section VIII. Other Information

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

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