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.

IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:

1. NIH ASSIST
2. An institutional system-to-system (S2S) solution
3. Grants.gov Workspace

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to stimulate research to understand the link between social disconnection – including both objective social isolation as well as perceived social isolation (otherwise known as loneliness) – and suicidal thoughts and behaviors in late-life. For the purposes of this NOFO, social disconnection can be characterized by structural components (e.g., objectively few social relationships or infrequent social contact, whether driven by individual choice or societal forces), functional components (e.g., low or insufficient levels of social support and feelings of being excluded), and qualitative components (e.g., perceptions that relationships are of poor quality or are dissatisfying).

Of specific interest is research that identifies mechanisms by which social disconnection confers risk for, and social integration protects against, suicidal thoughts and behaviors in late life. Putative mechanisms exist at multiple levels of analysis, including but not limited to neurobiological, behavioral, and environmental. Investigators are encouraged but not required to consider units of analysis within the Research Domain Criteria (RDoC).

Of particular interest is research that identifies neurobiological, behavioral, psychosocial, or environmental mechanisms that can be targets within an experimental therapeutics approach (e.g., the NIH Stage Model) intervention development or that can point to ways to modify existing healthcare and community-based services to better provide support for individuals in late-life in the midst of a suicidal crisis.

Background

In late adulthood, suicide rates are higher than in any other age group and have risen over 40% in the past ten years (National Center for Health Statistics). Late life suicide attempts are also the most likely to be fatal. Older adults are also disproportionately likely to be socially disconnected. In addition to exiting the workforce (i.e., through retirement or layoffs) and experiencing high rates of bereavement, many also endure functional limitations and reduced mobility, which limit in-person social interactions, suffer visual and hearing impairments which make digitally-mediated social interaction difficult or impossible, and experience deficits in core cognitive domains which degrade overall social functioning. Indeed, nearly a quarter of Americans over the age of 65 living in community settings are socially disconnected. Objective social isolation – i.e., the objective state of having few social relationships or infrequent contact with others– is associated with as much as a 3-fold greater risk of suicide in middle and late life. Perceived social isolation, or loneliness – i.e., a subjective feeling of being isolated that typically occurs when there is a discrepancy between one’s perceived and desired social relationships – doubles the odds of experiencing suicidal thoughts in late life. Overall, social disconnection is reported to be one of the primary motivators of self-harm in older adults.

Suicide prevention and intervention efforts that target the aging U.S./ population – a population most vulnerable to suicide – are urgently needed. Yet the evidence base for interventions that leverage social connection to prevent or treat late-life suicidal thoughts and behaviors must be further developed, beginning with mechanistic research that identifies potential intervention targets. At present, the evidence remains insubstantial regarding mechanisms which link social disconnection and late-life suicidal thoughts and behaviors. How does social disconnection put individuals at risk for suicidal thoughts and behaviors in late life? How does social integration protect against or ameliorate late-life suicide risk? How do suicidal thoughts and behaviors disrupt opportunities for social connection in late life that protect against suicide attempts? Important questions also remain regarding how individual factors such as sex and gender, race and ethnicity, socioeconomic status and cultural norms around death and dying and how they interact with environmental and structural factors such as urban vs rural setting, and community resources and supports to either confer or prevent risk. In addition, how the intersection of both individual and community/structural factors moderate the association between social disconnection and suicide risk in late life. Mechanisms by which healthcare and community-based services can be improved to support older adults experiencing a suicidal crisis are an additional area where further research is needed.

Research Objectives

This NOFO is intended to support research designed to identify the neurobiological, behavioral, and social mechanisms underlying social isolation and social disconnection with consideration for the identification of novel targets for future development of prevention and intervention efforts. Studies that leverage concepts, methods, and findings emerging from research on mechanisms in social isolation, social disconnection, and both as predictors of risk/resilience are encouraged.

Clinical research should target populations that would be at risk for suicidal thoughts and/or behaviors or intentional self-harm to examine mechanisms relevant to both social disconnection and suicidal thoughts and behaviors to examine mechanisms relevant to both social disconnection and suicidality. Applications submitted to this NOFO that are designated as clinical trials must be mechanistic clinical trials, as defined in NOT-MH-19-006. Clinical trials that propose to influence a clinical outcome, test safety or feasibility of an intervention, demonstrate the clinical efficacy or effectiveness of an intervention, or analyze the effect size of an intervention on clinical outcomes are ineligible for this NOFO.

Research is encouraged that addresses issues of health equity and health disparities in late life social connection and suicide, particularly work that adopts the NIA Health Disparities Research Framework. Research is also encouraged that adopts an intersectionality framework (i.e., a framework that addresses the multiple dimensions of individuals’ identity and social systems as they intersect with one another).

Research is encouraged that assesses symptoms relevant to mental disorder, and well-being, and suicide dimensionally, integrates across multiple levels of analysis (including but not limited to brain-level measurements), and employs cutting-edge methodology from fields such as cognitive and affective neuroscience, neuroimaging, neurophysiology, neuroendocrinology, lifespan psychology, and geroscience.

An RDoC approach encourages taking a dimensional perspective with respect to assessing human functioning psychopathology and concentrating on aspects of behavior and brain function that span a range from intact to gradations of impairment, independent of diagnosis. Thus, in such an approach, recruitment and eligibility of study participants need not be determined on the basis of traditional diagnostic categories, but should instead be based on criteria that result in a sample that is optimized to study the clinical phenomena of interest over their full range of variability. Such an emphasis on understanding the full dimensionality of neurobehavioral functioning generally precludes simple, dichotomous designs comparing patients versus controls. However, it is not inconsistent with the RDoC approach to additionally characterize transdiagnostic samples of participants recruited to represent the clinical phenomena of interest across the full range of variability, into existing diagnostic criteria. – this allows investigators to draw links from novel approaches of characterization and classification to existing diagnostic categories and extant research. Under this NOFO, if study hypotheses and/or enrollment criteria are not based on existing diagnostic criteria (i.e., an RDoC or other dimensional construct is proposed to serve as the primary variable representing psychopathology), the study design and sampling plan must be such as to assure that an adequate number of individuals assessed as falling within the more severely impaired ranges of that dimension will be included in the study. Varied research paradigms may be useful for pursuing the goals outlined above. Use of NIMH's RDoC  framework, or of RDoC-compatible approaches, in assessing component aspects of health, well-being, psychopathology and/or related domains of brain function dimensionally is not required but encouraged. If taking an RDoC approach, projects should employ assessment methods that converge on the construct from at least two levels of analysis. RDoC units of analysis (potential levels of measurement) include genes, molecules, cells, circuits, physiology, behavior, and self-report.

Applicants who propose to examine dimensional constructs that do not appear in the NIMH RDoC matrices but which are consistent with the central tenets of the RDoC initiative should cite substantial evidence for the validity of such constructs, and indicate strong theoretical support that the construct maps onto a specific biological system, such as a brain circuit or physiological pathway, thought to be involved in aspects of suicidality, though measurement of those brain circuits or physiological pathways as part of proposed research projects is not a requirement of this NOFO).

If the proposed research involves neuroimaging methods, applicants are encouraged to incorporate the use of protocols from the Human Connectome Project, assuming that the research addresses constructs that have been previously examined in the Human Connectome Project and that such protocols are available to the investigator.

Applicants are also strongly encouraged to review the Notice on enhancing the reproducibility of NIH-supported research through rigor and transparency (NOT-OD-15-103) and to incorporate appropriate features into the proposed research plans. NIMH has published guidelines for reporting elements of rigor in experimental design in applications (NOT-MH-14-004), and examples of critical elements for a well-designed study are summarized on the NIMH website.

Specific Areas of Interest

National Institute of Mental Health

Areas of interest include, but are not limited to:

• Improved understanding of the neurobiological and behavioral mechanisms underlying social isolation and social disconnection as it relates to suicidal behavior among older adults.
• Identification of social disconnection factors that increase risk of suicide in late life and/or the modality or lethality of suicidal behavior. Comparisons between the following dimensions of social connection are encouraged:
  • Functional dimension of social connection (e.g., the functions provided or perceived to be provided by social connections such as social support, means restriction, loneliness)
  • Structural dimension of social connection (e.g., social- and societal-level variables related to social connectedness such as relationship status, living arrangement, the natural and built environments (e.g., urbanicity/rural status), structural discrimination (including racism, sexism, ageism, and heterosexism), job loss/retirement, social capital, policy, healthcare delivery system, access, and quality, stigma)
  • Qualitative dimension of social connection (e.g., perceptions of positive and negative aspects of social connectedness such as relationship satisfaction, relationship strain, conflict)
• How biological, genetic, psychosocial, and environmental factors, including but not limited to mental health history, age, race, ethnicity, zip code, socioeconomic status, gender identity, disability, and marital status, impact social connectedness and risk for late-life suicide. Studies examining how the impact of social disconnection on suicide risk varies across populations of older adults, including in sexual, gender, racial, and ethnic minorities, and as a function of environmental contexts, such as community-dwelling versus assisted living status are encouraged.
  • Research is encouraged that addresses issues of health equity and health disparities in late life social connection and suicide, particularly work that adopts the NIA Health Disparities Research Framework. Research is also encouraged that adopts an intersectionality framework (i.e., a framework that addresses the multiple dimensions of individuals’ identity and social systems as they intersect with one another).
• Identification of brain circuits and/or neurobiological systems that may be modified by social connections and are mechanisms of pathophysiology or can be targets for the development of treatments that can prevent suicidal behavior among older adults.
• Studies that examine the role of structural barriers to social connection across different older adult communities that may predispose to enhancing risk of suicide.
• Studies that examine the intersectionality of both structural and societal barriers to connection and their impact on vulnerable elders.
• Studies that construct and validate assessments for social isolation and social disconnection in primary care and emergency departments and develops clearly defined taxonomies of social disconnection to enhance communication among members of integrative care teams who provide care to patients considering suicide in late life
• Computational approaches to identify predictive and/or explanatory causal patterns of factors associated with social isolation and suicidal behavior.
• Explore how mechanisms in social disengagement trajectories may be affected by older adult community service outreach efforts (e.g., nutrition support programs; home healthcare, etc.).
• Mechanisms by which social connections may be modified to prevent suicidal thoughts and behaviors.

The companion R01 grant mechanism of this NOFO (PAR-25-067) encourages longer term applications with preliminary data.

The following research activities are non-responsive to this NOFO, and will not be reviewed:

• Studies whose purpose is to evaluate safety, clinical efficacy, effectiveness, and management; and/or development or implementation of new interventions. See the NIMH Clinical Trials website and NOT-MH-19-006 for further details about submission of mechanistic clinical trials to NIMH see NOT-MH-20-105
• Studies that are descriptive and do not address mechanism
• Studies that assess mechanisms of social disconnection and late-life suicidal thoughts and behaviors at only a single level of observation and analysis (i.e., without combining multiple levels/methods such as genetic, cellular, brain circuit, physiological, behavioral, self-report)
• Studies that address only social disconnection in late life (in the absence of measuring risk for or experience of suicidal thoughts or behaviors) or that address only late-life suicide (in the absence of assessing social factors)
• Nonhuman animal studies

The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring (NOT-MH-19-027). The application’s PHS Human Subjects and Clinical Trials Information, including the Data and Safety Monitoring Plan, should reflect the policies and guidance in this notice. Plans for the protection of research participants and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.

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 Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 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 for additional information.

• 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 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.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to: [email protected]

Page Limitations

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.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Research Strategy: Applicants must include the following sections as part of the Research Strategy. Applications should not duplicate information provided in the attachment described in the PHS Human Subjects Clinical Trial Information form but may reference it to provide context as needed.

Factor 1. Importance of the Research

Significance:

• Discuss the likelihood that the project will contribute to improving the understanding of the link between both social connectedness/disconnection and suicidality.

Factor 2. Rigor and Feasibility

Approach:

• If taking an RDoC approach, describe assessment methods that converge on the construct from at least two levels of analysis (e.g., genes, molecules, cells, circuits, physiology, behavior, and self-report).
• As part of the conceptual framework, indicate clear mechanistic hypotheses and have adequate capacity to test and potentially refute the hypotheses.
• If using a dimensional construct, the study design and sampling plan must include an assurance  that an adequate number of individuals falling within the more severely impaired ranges of that dimension will be included in the study.
• Describe plans for assessing comorbid medical conditions and controlling or accounting for their potential confounding influence.
• For mechanistic clinical trials, discuss how the study design addresses whether the intervention engages the mechanism(s) presumed to underlie the intervention effects. Explain plans for assessing target engagement/mechanisms. Detail how the data analysis will determine whether intervention-induced changes in target(s) are associated with intended outcomes. Applications should clearly state the rationale for the selection of suicide-related constructs and corresponding assessment instruments, the time periods assessed, and the schedule for assessments. For studies enrolling human subjects, address the provisions for clinical management when suicidal behavior is reported.

Factor 3. Expertise and Resources 

Investigators:

• In the biosketches, provide evidence that the investigative team has adequate expertise in studying both social connectedness/disconnection and suicidality.
• For projects that propose to enroll human participants, detail how investigators are appropriately prepared to address clinical, ethical, and safety considerations necessary when conducting research with participants at elevated risk for suicide.

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:

In keeping with NIH's goals to enhance transparency of reporting and enable reproducible and translatable discovery research, applicants are expected to make all data, analytical methods and outputs, and research tools available to the broad scientific community prior to publication. Data is defined as the final data on which a publication is based, usually presented in summary form in a publication. These may include image libraries, video, and audio recordings, or other derivatives of data that are relevant to the research being reported. In general, sufficient materials should be made available to allow replication and/or productive secondary analysis of the data. Thus, it is expected that raw data or minimally processed data would be shared.

• 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.

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this NOFO are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100). Established by the NIMH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this NOFO are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of preparing and transferring data to the DCC for submission to the NDA. The NDA web site provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Estimation Tool which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this NOFO prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied. For more guidance on submitting data to NDA refer to the NDA web site and give the link to the following site https://nda.nih.gov/contribute/contribute-data.html. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

Applicants are encouraged to include appropriate support for annotation and curation of the molecular and clinical data types used and/or generated on the project to maximize the usability of the data by the broader research community for various types of meta-analyses and systems biology research.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- 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 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.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

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

4. Submission Dates and Times

Part I. 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 How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

NIMH expects investigators for this funding announcement to collect Common Data Elements (CDEs) for mental health human subjects research. Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications involving human research participants. The necessary funds for collecting and submitting these CDE data from all research participants to the NIMH Data Archive (NDA) should be included in the requested budget. A cost estimator (https://nda.nih.gov/ndarpublicweb/Documents/NDA_Data_Submission_Costs.xlsx) is available to facilitate the calculation of these costs. NIMH may seek further information regarding CDEs prior to award. Additional information about CDEs can be found at the NIMH webpage on Data Sharing for Applicants and Awardees.

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 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 organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply Application Guide.

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

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].

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 R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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 scored 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 evaluate 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 criterion score. 

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.

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 the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

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:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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 applicant’s 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 applicant’s 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.

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

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 recipient’s 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.

The NIMH has published policies and guidance for investigators regarding human research protection, data and safety monitoring, Independent Safety Monitors and Data and Safety Monitoring Boards, reportable events, and participant recruitment monitoring (NOT-MH-19-027). The application’s PHS Human Subjects and Clinical Trials Information should reflect the manner in which these policies will be implemented for each study record. These plans will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations. The NIMH will expect clinical trials to be conducted in accordance with these policies including, but not limited to: timely registration to ClinicalTrials.gov, submission of review determinations from the clinical trial’s data and safety monitoring entity (at least annually), timely submission of reportable events as prescribed, and establishment of recruitment milestones and progress reporting.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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.

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. 

Not Applicable

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.

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 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.

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: [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]

Jovier Evans, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-6328
Email: [email protected]

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

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]

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 2 CFR Part 200.