HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed)

HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH) / National Institute on Drug Abuse (NIDA). This NIH HEAL (Helping to End Addiction Long-term) Initiative grant focuses on supporting research to identify novel targets for the prevention and treatment of opioid use disorders and overdose.

This R01 grant supports investigator-initiated research projects.

Expired RFA-DA-24-063: HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (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 on Drug Abuse ( NIDA ) National Institute of Allergy and Infectious Diseases ( NIAID ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title HEAL Initiative: Novel Targets for Opioid Use Disorders and Opioid Overdose (R01 Clinical Trial Not Allowed) R01 Research Project Grant 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 .

Notice of Funding Opportunity (NOFO) Number Companion Funding Opportunity Exploratory/Developmental Grants See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) 93. 279, 93. 855, 93.

213, 93. 866, 93. 865 Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to support research focusing on the identification of druggable new targets and the discovery of optimizable probes for the development of safe and efficacious medications to prevent and treat opioid use disorders (OUDs), opioid overdose, and opioid-polysubstance use comorbidities.

This NOFO is part of the NIH Helping to End Addiction Long-term (HEAL) initiative to accelerate the development of novel medications to treat all aspects of the opioid addiction cycle, including progression to chronic use, withdrawal symptoms, craving, relapse, and overdose. For information about Novel Therapeutic Options for Opioid Use Disorder and Overdose, see https://heal. nih.

gov/research/medication-options This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn. Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material .

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 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.

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 NIH HEAL Initiative: This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management.

More information about the HEAL Initiative is available at: https://heal. nih. gov/.

There is an ongoing opioid use and overdose crisis in the United States. Opioids that are often prescribed for the treatment of pain can lead to opioid misuse and Opioid Use Disorders (OUDs). It has been reported that more than 3 million Americans have OUDs, and many started their addiction with prescribed opioids.

One of the most devastating consequences of opioid misuse is opioid overdose, which can produce respiratory depression and death. Drug overdose is a leading cause of accidental death in the US, with more than 80,000 opioid-involved overdose deaths reported in 2021.

Although safe and effective pharmacotherapies for the treatment of opioid use disorders and for the prevention or reversal of opioid overdose are available, there are limitations to their use, and they are underutilized. For example, methadone and buprenorphine are opioid agonist therapies and, as such, have policy restrictions on their use in treating OUD.

The opioid antagonist naloxone is not optimally effective for the reversal of overdoses of highly potent opioids such as fentanyl.

Therefore, there is an urgent need to develop new medications through the identification of novel targets and lead molecules to enable the development of new therapeutic approaches that will be effective at various stages along the trajectory of OUD from initiation to chronic use, physical dependence, relapse, and overdose.

Recent research using new technologies has advanced our knowledge of how opioids produce their many effects, from molecular to circuit-level analysis. A variety of methods have been developed as enabling techniques to interrogate signaling pathways and to identify/validate druggable targets of interest.

These include single-cell multiomics, high-throughput chemotranscriptomics, genetically encoded biosensors, CRISPR-based approaches, targeted protein degradation, click chemistry, and the use of genetically modified organisms and animal models.

The application of these emerging technologies along with nonbiased approaches provides an opportunity to identify novel targets encompassing enzymes, receptors, ion channels, intracellular trafficking, neuropeptides, signaling pathways and networks, protein-protein interactions, genetic and epigenetic targets, or other biological mechanisms of relevance to OUDs and opioid overdose.

Parallel advances in drug development technologies, such as the ability to screen large synthetically accessible or available libraries of compounds, including DNA encoded libraries, virtual screening of ultra-large libraries of molecules, and the application of computational tools, machine learning methods, and artificial intelligence have the potential to shorten the time needed for identifying probe molecules for interrogating the targets as well as for optimization of the probes and lead molecules toward the drug development path.

The developments in target identification coupled with the advances in ligand discovery/optimization approaches provide an unprecedented opportunity to accelerate the development of drugs for the treatment of OUDs and opioid overdose.

The purpose of this notice of funding opportunity (NOFO) is to support such studies leading to the identification of druggable new targets and the discovery of optimizable probes for the development of safe and efficacious medications to prevent and treat OUDs and opioid overdose.

This program announcement is specifically focused on the identification of novel targets and preclinical validation of small molecules and biologics for treating OUDs, opioid overdose and opioid-polysubstance use comorbidities. The outcome sought by the National Institute on Drug Abuse (NIDA) is to expand the target space and lead molecules to enable the development of novel therapeutic approaches.

The main focus of research activities to be supported through this NOFO is the identification of novel drug targets and their validation through the development of probe molecules that modulate those targets. Applications may focus on hit identification/confirmation up to the lead optimization stage.

The proposed studies could include, but are not limited to, the following: Identification of novel targets for the treatment of OUDs, opioid overdose, and opioid-polysubstance use comorbidities. Compound screening (including FDA-approved drugs) to identify new hits and leads. Development of artificial intelligence/machine learning methods for the identification of novel targets and lead molecules.

Application of biophysical and computational methods, including virtual screening, machine learning, and artificial intelligence to identify targets, hits, leads, and optimization of hits to leads. Discovery and development of small molecule probes and lead compounds for specific novel targets that have been identified as promising targets for OUD and opioid overdose.

Studies on the interaction of the hits and probe molecules with the identified targets/pathways. Identification of peptides, biologics (monoclonal antibodies, recombinant proteins), and nucleic acid-based molecules to modulate the expression or function of the identified targets. Studies on target engagement in vivo , mechanism of action, and target selectivity.

Testing the identified probes and lead compounds in appropriate animal behavioral models of OUD or opioid overdose. Applications that include the following types of studies will be considered non-responsive and will not be reviewed: Applications focusing on targets for the discovery of analgesics for the treatment of pain. Applications focusing on optimization of leads to clinical candidates and drug development efforts.

Applications focusing on the generation of new animal models. Applications that do not focus on the discovery of novel targets or probes for OUD/opioid overdose, or targets involved in comorbidities associated with the use of opioids in combination with other substances. Information Relevant to Specific Institutes/Centers/Offices: The participating NIH institutes and centers are interested in applications with a specific research focus.

Specific research areas of interest to the participating NIH institutes are listed below.

National Institute of Allergy and Infectious Diseases (NIAID) In addition to the ongoing opioid use and overdose crisis, synthetic opioids, such as fentanyl, carfentanil, acetylfentanyl, sufentanil, remifentanil, lofentanil, and alfentanil, have also been designated by the U.S. Government as highly toxic chemicals of concern where medical countermeasures (MCMs) are urgently needed to advance national biosecurity and medical and public health preparedness for, response to, and recovery from disasters and mass casualty emergencies resulting from deliberate and/or accidental release.

Through the Chemical Countermeasures Research Program ( CCRP ), the NIAID supports the research and early stage development of MCMs to treat and/or prevent serious morbidities and mortality during or after high consequence public health emergencies involving the release of highly toxic chemicals that may result in mass civilian casualty.

In partnership with the NIDA Chemistry and Pharmacology Branch ( CP ), the CCRP is particularly interested in identifying novel therapeutic targets and approaches that: Will improve upon the current post-exposure/overdose standard-of-care therapies to more effectively rescue victims of synthetic opioid intoxication alone or in combination with other substances, such as xylazine and nitazenes.

Can be easily and rapidly deployed in the field, i.e., amenable to mass casualty use. May be therapeutically effective against one or more of the synthetic opioids of concern listed above. Has a mechanism of action other than antagonizing the mu-opioid receptor.

Improves respiratory drive to stimulate reversal of opioid-induced respiration depression (OIRD). National Center for Complementary and Integrative Health (NCCIH) The National Center for Complementary and Integrative Health (NCCIH) supports a broad portfolio of basic and mechanistic projects on natural products and their potential in multicomponent interventions.

These natural products include microbial-based therapies such as probiotics, prebiotics, botanicals, and dietary supplements. In the context of this RFA, NCCIH is particularly interested in applications pertinent to the development of microbial-based therapies as an approach for the prevention and treatment of OUDs, opioid overdose, and opioid-polysubstance use comorbidities.

The proposed studies could include, but are not limited to: Identification and verification of novel targets for microbial-based therapies with relevance to the gut-brain axis. Discovery of microbial-based therapies for specific novel targets that have been identified as promising targets for OUDs, opioid overdose, and opioid-polysubstance use comorbidities.

Studies to characterize the underlying mechanisms of microbial-based therapies for the purpose of identifying new therapeutic targets. Discovery of microbial-based therapies as complementary interventions with existing therapies.

Plan for Enhancing Diverse Perspectives (PEDP) This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310 , submitted as Other Project Information as an attachment (see Section IV). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material .

The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions. Other application considerations Applicants with preliminary data may wish to apply for this R01 NOFO. High risk/high payoff projects that lack preliminary data are most appropriate for the companion R21 NOFO RFA-DA-24-064 .

The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.

In addition to scientific diversity, applicants should strive to incorporate diversity in their team development plan. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems.

There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.

In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral, and social sciences.

Please refer to Notice of NIH's Interest in Diversity NOT-OD-20-031 for more details. Engaging People with Lived Experience and Other Collaborators People with lived experience (e.g., patients, patient advocates, caregivers, families, community leaders) have important insights that can improve meaningful outcomes, uptake of research findings, and health equity across the continuum of research from basic through implementation studies.

The perspectives of other relevant collaborators (e.g., health service providers, payers, public health agencies, community-based organizations, biotech, pharma) can further improve research impact. The NIH HEAL initiative strongly encourages applicants to specify their plan for meaningful engagement of people with lived experience and other collaborators in the research process.

Meaningful engagement will vary with the focus of the research but should at minimum ensure that researchers are connecting with relevant collaborators and incorporating their perspectives throughout the conception, implementation, and dissemination of the research. Meaningful engagement should address what the researchers will learn and how the people with lived experience and/or collaborators will benefit from the partnership.

To promote health equity, as is relevant for the research proposed, it is recommended that at least two people with lived experience from populations who experience health disparities should be meaningfully engaged in these efforts. See this resource for more information in engaging people with lived experience: https://aspe. hhs.

gov/lived-experience . Pre-Application Consultation Applicants are strongly encouraged to discuss their interests with Scientific/Research contacts well in advance of submitting applications. This early contact will provide an opportunity to discuss and clarify NIH policies and guidelines, including the scope of the project relative to the HEAL initiative mission and intent of this funding opportunity announcement.

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 Resubmission - Resubmissions of applications previously submitted to RFA-DA-22-031 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 NOFO.

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 NIH HEAL (Helping to End Addiction Long-term) Initiative intends to commit an estimated total of $5 million to fund 8-10 awards in response to this and the companion notice of funding opportunity in FY 2024.

Awards pursuant to this funding opportunity are contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are limited to $400,000 in direct costs per year and need to reflect the actual needs of the proposed project. 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 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 Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registration; 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.

Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 .

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide. This NOFO 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 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. 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] All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO. 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, with the following exceptions or additional requirements: Plan for Enhancing Diverse Perspectives (PEDP) In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.

The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section.

The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review.

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to: Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based). Description of any planned partnerships that may enhance geographic and regional diversity.

Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce. Proposed monitoring activities to identify and measure PEDP progress benchmarks. Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.

Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds. Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s). Publication plan that enumerates planned manuscripts and proposed lead authorship.

Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds. For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see https://braininitiative. nih.

gov/about/plan-enhancing-diverse-perspectives-pedp . 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.

PEDP implementation costs: Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants. nih. gov/grants/policy/nihgps/html5/section_7/7.

1_general. htm ). 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. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

HEAL Public Access and Data Sharing Policy: NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing and immediate access to publications ( https://heal. nih. gov/about/public-access-data ).

Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal. nih. gov/data/complying-heal-data-sharing-policy .

Resources and tools to assist with data related activities can be found at https://www. healdatafair. org/.

For more detail and specific data sharing requirements, see Section 4. Other plans. Publications resulting from NIH HEAL Initiative funded studies must be immediately publicly available upon publication.

For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The HEAL Initiative has additional requirements that must be addressed in the Data management and Sharing plan. All HEAL-generated data must be shared through the HEAL Initiative Data Ecosystem following HEAL’s compliance guidance ( https://heal.

nih. gov/data/complying-heal-data-sharing-policy ). Specifically, HEAL applicants must include: Plans to submit data and metadata (and code, if applicable) to a HEAL-Compliant data repository ( https://www.

healdatafair. org/resources/guidance/selection ) and follow requirements of the selected repository Plans to register your study with the HEAL platform within one year of award ( https://heal. github.

io/platform-documentation/study-registration/ ) Plans to submit HEAL-defined study-level metadata within one year of award ( https://github. com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans. pdf ) and https://heal.

github. io/platform-documentation/slmd_submission/ ) To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subject are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program ( https://heal. nih.

gov/data/common-data-elements ) if applicable and relevant to their research. Studies using CDEs, regardless of whether they are part of the HEAL repository, will be required to report which questionnaires are being used. To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms.

HEAL has developed additional details and resources to fulfill these requirement ( https://www. healdatafair. org/resources/road-map ).

HEAL Public Access and Data Sharing Policy: NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing and immediate access to publications ( https://heal. nih. gov/about/public-access-data ).

Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal. nih. gov/data/complying-heal-data-sharing-policy .

Resources and tools to assist with data related activities can be found at https://www. healdatafair. org/.

For more detail and specific data sharing requirements, see Section 4. Other plans. Publications resulting from NIH HEAL Initiative funded studies must be immediately publicly available upon publication.

For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests 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 at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed. Note: Delayed onset does NOT apply to a study that can be described