Neuromodulation/Neurostimulation Device Development for Mental Health Applications (R01 Clinical Trial Not Allowed)

Neuromodulation/Neurostimulation Device Development for Mental Health Applications (R01 Clinical Trial Not Allowed) is sponsored by National Institute of Mental Health (NIMH), NIH. This Notice of Funding Opportunity (NOFO) encourages applications seeking to develop the next generation of brain stimulation devices for treating mental health disorders.

Expired PAR-22-039: Neuromodulation/Neurostimulation Device Development for Mental Health Applications (R01 Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. 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 Neuromodulation/Neurostimulation Device Development for Mental Health Applications (R01 Clinical Trial Not Allowed) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity November 21, 2024 - This PAR has been reissued as PAR-25-287 effective January 8, 2025.

NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109 Funding Opportunity Announcement (FOA) Number 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 funding opportunity announcement (FOA) is to encourage applications seeking to develop the next generation of brain stimulation devices for treating mental health disorders.

Applications are encouraged that will either 1) develop novel brain stimulation devices or 2) significantly enhance, by means of hardware/software improvements, the effectiveness of brain stimulation devices that are currently U.S. Food and Drug Administration (FDA)-approved or cleared.

Novel devices should move beyond existing electrical/magnetic stimulation and develop new stimulation techniques capable of increased spatiotemporal precision as well as multi-focal, closed-loop approaches. Applications seeking to develop new capabilities should focus on significant enhancement of the spatial resolution, depth of delivery, and/or precision of the device .

Incremental changes to existing devices (e.g., software updates) are not within the scope of this announcement. Applications should be submitted by multi-disciplinary teams with diverse expertise including systems neuroscience, engineering, clinical, and regulatory affairs.

Applications submitting in response to this FOA should promote the development or significant enhancement of novel tools (hardware/software) for brain stimulation in humans. Although the application should focus on the engineering development and bench top testing of the tool, animal and limited human testing necessary to demonstrate initial proof of concept is allowable.

Applications to this FOA are not expected to be hypothesis-driven, but should propose design-directed, developmental, or discovery-driven technology research using integrative approaches. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) The following table includes NIH standard due dates marked with an asterisk.

Renewal / Resubmission / Revision (as allowed) All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s). 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 SF424 (R&R) Application Guide ,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) 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.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

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.

Funding Opportunity Description The use of brain stimulation devices provides a unique opportunity to develop novel treatments for mental health disorders. Brain stimulation devices provide both the most efficacious (electroconvulsive therapy, ECT) and one of the most recently-cleared (transcranial magnetic stimulation, TMS) treatments for depression.

However, while these successes demonstrate the potential to improve clinical care, limitations of the few existing FDA approved/cleared devices (e.g., cognitive side effects of ECT, variability in response to TMS) hamper widespread clinical use.

In order to develop efficacious treatments that will be widely utilized across a variety of disorders, the development of innovative brain stimulation devices and novel approaches with existing devices is urgently needed New devices, developed with a focus on aspects unique to mental health indications, are needed to fully explore the potential of brain stimulation treatments.

The majority of clinical studies using brain stimulation therapies for mental health disorders utilize existing devices developed for other neurological conditions. Deep brain stimulation (DBS) and vagal nerve stimulation (VNS) electrodes were developed for the treatment of Parkinson’s Disease and epilepsy. They have subsequently been studied, with minimal to no modification, for use in mental health disorders with mixed results.

New devices, whose development is informed by basic and clinical science findings in mental health research, may provide improved treatments for patients. For example, while current DBS electrodes are limited to one or two stimulation sites, neuroimaging studies have demonstrated the distributed, network-based nature of mental health disorders.

Therefore, distributed, multi-focal electrode arrays may be necessary to modulate networks back into a desired state. New forms of energy (e.g., ultrasound) also have the potential to be incorporated into the next generation of brain stimulation devices. In addition to the development of new devices, significantly enhancing the capabilities of existing devices presents an opportunity to improve clinical care.

While drug treatments become static (in terms of chemical composition) once developed, brain stimulation devices are amenable to hardware/software changes that can readily translate to improved patient care. Examples of these approaches include development of real time electric field (e-field) modeling software and augmented reality delivery systems to enable practitioners to interactively target regions of interest with TMS.

The ability to close the loop with a brain stimulation device and neuroimaging/recordings could also result in improved clinical outcomes. Improved devices that focus on developing novel approaches to delivery of previously demonstrated effective treatments are also of interest.

Although ECT provides the best remission rates for depression, the widespread generalized seizure induced by the device produces cognitive side effects that limit its use. The development of novel devices that deliver more focused stimulation resulting in a smaller, controllable seizure, may produce high levels of response while minimizing side effects.

Additionally, approaches that improve the focality, depth, or closed-loop delivery of TMS could improve response rates. This funding opportunity announcement (FOA) encourages the development of novel brain stimulation devices and accompanying software/hardware additions that enable improved delivery of brain stimulation treatments for mental health indications.

Applications should be submitted by multi-disciplinary teams with expertise in systems neuroscience, engineering, clinical, and regulatory affairs and promote either the development of novel tools (hardware/software) or significant enhancement of existing tools (hardware/software). Applications should be engineering/pre-clinical based and focus on hardware and software development and validation.

Although the application should focus on the engineering development of the tool, animal and limited, non-clinical trial, human testing to demonstrate initial proof of concept is allowable. Applications that seek to study specific scientific or clinical hypotheses that utilize devices are outside the scope of this FOA. Applications may propose to develop novel invasive or non-invasive brain stimulation devices.

New devices should be designed to significantly advance the field and go beyond current stimulation and low-channel count recording/stimulating capabilities. Existing magnetic and electrical stimulation methods have limited spatial and temporal precision. To overcome these obstacles and move beyond incremental advances, collaborations between physicists, engineers, neuroscientists, and clinicians are encouraged.

The perspective and expertise of such integrative teams could enable the development and testing of novel approaches that leverage other types of energy or stimulation methods in a way that can lead to novel tools for scientific discovery and for therapeutic brain stimulation.

Applications that propose to improve spatiotemporal precision, stimulate at depth, enable multi-focal recording/stimulation, and utilize novel stimulation paradigms are encouraged. Appropriate modeling and preliminary data should be presented to demonstrate the feasibility of the stated approach.

While the application may be in the initial stages of device development and may therefore still be in the animal testing phase, the proposed tools and methods must be designed for use in humans. Animal testing should focus on questions of safety. Industry partnership is encouraged and should be detailed in the application.

The regulatory process for the new technology should be described in the application, when applicable. Applications may also propose to develop additional capabilities for existing FDA-approved or cleared brain stimulation devices and related technologies. However, proposed improvements to existing devices and related technology should be significant and innovative, rather than incremental.

Appropriate improvements may include: 1) incorporating advanced approaches to stimulation delivery, such as real-time realistic head/electric field modeling that incorporates patient-specific tractography or cellular-level resolution; 2) synchronizing behavioral recordings with brain recordings in novel ways; or 3) developing novel delivery methods, such as augmented and virtual-reality approaches.

For existing devices, approaches that seek to improve the focality and depth of stimulation, controllability of the delivered dose, sham control delivery, or recording capabilities are encouraged. Software approaches that seek to develop novel approaches (e.g., machine learning) to biomarker-driven targeted delivery of stimulation are also encouraged.

Topics of interest for this FOA include, but are not limited to: Multi-focal electrode interfaces. These devices should demonstrate the capability to record and stimulate distributed brain regions implicated in mental health disorders. Devices capable of both recording and stimulating neural activity, with the ability for closed-loop control.

These devices should be able to demonstrate clear capability to record oscillations of interest to mental health applications. Improved capabilities to synchronize behavioral data with neural data. Dense behavioral phenotyping is now possible, both in the lab and in naturalistic environments.

The ability to temporally synchronize large behavioral data sets with large neural data sets is of high priority. Devices that enable targeted stimulation via optogenetic (or other circuit therapeutic) techniques in humans. Next-generation ECT devices that more focally deliver energy for controllable seizure generation.

Validation of novel approaches, such as transcranial ultrasound for neuromodulation to stimulate the brain focally. A wireless, miniaturized, portable, and closed-loop EEG-stimulation system. Ideally, this should be of a size to be easily worn (i.e., fits comfortably inside a baseball cap).

Improved portability of brain stimulation devices, without reduction in targeting capabilities. Pre-clinical studies necessary to obtain regulatory approval for human testing. Development of higher spatial resolution realistic head modeling approaches that improve the delivery of FDA-cleared treatments, such as TMS.

Improved focality and depth of stimulation, along with controllability for FDA- approved or cleared devices for a particular indication. Development of closed-loop recording and stimulating for non-invasive devices, such that imaging/recording informs active stimulation. Software approaches, such as machine learning, that incorporate patient-specific biomarkers into brain stimulation treatment algorithms.

New approaches to sham conditions that enable more reliable controlled trials. Topics of lower program priority include: Applications that seek to study scientific or clinical hypotheses that simply utilize devices. Devices with low spatial resolution.

Models that focus on standard brains and are not specific to individual patient anatomy. Incremental improvements to existing devices, such as operating software system updates. Devices with no clear potential for human application.

Innovation in this biomedical engineering FOA has a broad definition that includes development of new methods, ideas, or tools, integration of existing components into new combinations that deliver greater capabilities, new efficiencies, and/or greater effects.

Applications to this FOA are not expected to be hypothesis-driven, but should propose design-directed, developmental, or discovery-driven technology research using integrative approaches.

Overall impact of these advances may include reducing disparities in care, promoting wellness and independent living, increasing access to and utility of technologies to improve quality of life, reducing cost and complexity of procedures, and increasing throughput, sensitivity, and specificity of diagnostic tests.

Applications seeking to explore scientific questions (in humans or animals) using novel brain stimulation devices should apply to the NIH Parent R01 ( PA-20-185 ) and NIH Parent Clinical Trial Required R21 ( PA-20-194 ), or NIMH R21 ( PA-21-235 ) Funding Opportunity Announcements.

Those seeking to assess devices as treatments in a clinical population should refer to the NIMH Policy for Submission of Applications Containing Clinical Trials ( NOT-MH-14-007) . NIMH Only Accepts Clinical Trial Applications Proposing Mechanistic Studies for Clinical Trial Parent R01 and R21 Announcements. See NOT-MH-19-006 for information on NIMH requirements.

All applicants are strongly encouraged to contact the designated Scientific/Research Contacts at NIMH prior to submission. Applicants who seek to establish proof-of-concept should respond to the companion R21 FOA, PAR-22-038 . Small businesses should consider applying to the SBIR/STTR programs to support the technology development.

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

Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed Renewal of PAR-18-942 and PAR-22-039 Resubmission of PAR-18-942 and PAR-22-039 Revision of PAR-18-942 and PAR-22-039 The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Only those application types listed here are allowed for this FOA. Not Allowed: Only accepting applications that do not propose clinical trials. 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 FOA. Section III.

Eligibility Information 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 (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 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 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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

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. eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration, but 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 DUNS number and 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 his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

Due to the transdisciplinary nature of the projects and the focus on collaboration and expertise sharing, this FOA requires the applicants to comprise a transdisciplinary team of investigators with expertise from fields such as engineering, device development, regulatory, physical, mathematical, computational sciences, as well as neuroscience, neuropsychiatry, and other areas of the biological sciences.

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

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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement 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 SF424 Application Guide and the Table of Page Limits must be followed.

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

For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages. The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. 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. Intellectual Property (IP) Strategy: Applications are expected to include an IP strategy, and the page limit must be no more than three pages.

Applications that exceed this limit will not be reviewed. This attachment should be entitled "IP Strategy. pdf".

Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable. A goal of this program initiative is to advance research towards the development of products that will benefit the public. Accordingly, applicants should describe the IP landscape surrounding their therapeutic device.

This should include any known constraints that could impede the development of their therapeutic device or diagnostic (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent and/or on the market, etc.) and how these issues could be addressed as appropriate and consistent with achieving the goals of the program.

If the applicant proposes using a device or technology whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any questions that may constrain or impede its ability to operate and move the technology forward consistent with achieving the goals of the program.

If patents pertinent to the therapeutic device being developed under this application have been filed, the applicants should indicate the details of filing dates, what types of patents are filed, application status, and associated United States Patent Office (USPTO) links, if applicable. Applicants should also discuss future IP filing plans.

For a multiple-PD/PI, multiple-institution application, applicants should describe how IP will be shared or otherwise managed, and the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed.

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

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 and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: The Research Strategy should clearly address the purpose of this FOA and indicate : How the proposed approach will use the concepts from engineering, physical science, computational or other multidisciplinary methods to address the biomedical problem identified in the application.

How the investigative team demonstrates sufficient depth and breadth of the multiple disciplines necessary to complete the project. Anticipated risks and limitations. Any animal or non-clincial trial human testing should be justified in the context of necessity for device development.

Any proposed work in animals must include a description of how the methods would be scaled up for use in humans. In recognition of the fact that these methods might be in early stages of development, work with human volunteers can, but does not need to, be included.

Applications should also include the following sections in the Research Strategy: Current State-of-the-Art: Applications should define the current state of technology as a benchmark against which their proposed new technology or improvements will be measured.

Given that projects are likely to be early-stage and high-risk in nature, this should include the specific proof-of-concept test(s) that will indicate whether/how a proposed tool actually "works", along with alternative strategies should that effort fail to perform as expected.

Tests should include a comparison against existing benchmark technologies; if a tool is truly first-in-class, comparisons may be done against a nearest neighbor technology. Investigators should briefly note how results will be used to inform future phases of tool development, such as testing in other model systems or in human brain. Applications should describe any relationship with industry/commercial partners.

This should include details on what, if any material, partners are providing. If a memorandum of understanding (MOU), confidential disclosure agreement (CDA), or collaborative research agreement (CRA) has been signed by both parties, this should be described by the applicant. Applications should describe the potential translational pathway for their devices.

This should include a description of the regulatory and reimbursement pathway for their device or specific type of technology. Future commercialization, implementation, and dissemination plans should be discussed. Project Milestones and Timeline: A timeline and milestones should be included that propose indicators of progress at critical junctures.

These should be tailored to the unique scope of each project and written concretely enough to evaluate what exactly will have been achieved (e.g., crucial steps in tool making) during the course of the project. Quantitative benchmarks for success should be included. A letter of support from any industry partners should be included.

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. All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. There is no prescribed single license for the distribution of standards produced through grants responding to this announcement.

However, the data sharing plan is expected to discuss: (1) how the standard will be made widely available; (2) transferability, i.e., ability of another individual or team to continue development as appropriate; (3) terms of availability that will enable researchers to enhance the standard and share those enhancements with colleagues.

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this FOA are expected to share those data via the National Data Archive (NDA; see NOT-MH-19-033 ). Established by the NIH, 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 FOA 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 data submission.

The NDA web site provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model 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 FOA 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.

The NDA Data Sharing Plan is available for review on the NDA website . NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary . Only limited Appendix materials are allowed.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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