Social Disconnection and Suicide Risk in Late Life (R01 Clinical Trial Optional)

Social Disconnection and Suicide Risk in Late Life (R01 Clinical Trial Optional) is sponsored by NIH NIMH. Encourages research addressing the link between social disconnection and suicidal thoughts and behaviors in late life.

PAR-25-067: Social disconnection and Suicide Risk in Late Life (R01 Clinical Trial Optional) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Mental Health ( NIMH ) Funding Opportunity Title Social disconnection and Suicide Risk in Late Life (R01 Clinical Trial Optional) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Exploratory/Developmental Grants See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this Notice of Funding Opportunity (NOFO) is to encourage research that addresses the link between social disconnection in late-life and late-life suicidal thoughts and behaviors.

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. Mechanisms to be considered exist at multiple levels of analysis, including but not limited to neurobiological, behavioral, and environmental.

This NOFO solicits R01 applications, while the companion announcement PAR-25-066 solicits R21 applications. High risk/high payoff projects that lack preliminary data may be most appropriate for the R21 mechanism. Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk.

Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

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

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

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

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description 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 Mode l) 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.

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 US 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 that 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, race and ethnicity, socioeconomic status, and cultural norms around death and dying interact with environmental and structural factors such as urban vs rural setting, and community resources and supports to either confer or prevent risk.

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.

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 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 disparities in late life social connection and suicide. 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.

The 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.

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), discrimination (including, sexism, and ageism), 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) Identification of social disconnection factors that increase risk of suicide in late life.

Examination of factors across dimensions of social connection, including functional (e.g., functions provided or perceived to be provided by social connections such as social support, means restriction, loneliness), structural (e.g., social- and societal-level variables related to social connectedness such as marital status and living arrangement, social capital, policy, healthcare delivery system), and qualitative (e.g., perceptions of positive and negative aspects of social connectedness such as relationship satisfaction, relationship strain, conflict) dimensions is encouraged.

How biological, genetic, psychosocial, and environmental factors, including but not limited to mental health history, age, race, ethnicity, zip code, socioeconomic status, 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 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 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 R21 grant mechanism of this NOFO (PAR-25-066 ) encourages shorter, higher-risk applications with little (or no) 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) 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 Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed Revision of RFA-MH-22-135, PAR-23-238 and PAR-25-066 Renewal of RFA-MH-22-135, PAR-23-238 and PAR-25-066 Resubmission of RFA-MH-22-135, PAR-23-238 and PAR-25-066 The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Optional: Accepting applications that either propose or do not propose clinical trial(s). Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 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.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

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

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Research Strategy : Applicants should 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 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 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. Will data analysis 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 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 the 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.

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