HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)

HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional) is sponsored by National Heart, Lung, and Blood Institute (NHLBI) / NIH HEAL Initiative. Supports action-oriented research under the NIH HEAL Initiative to accelerate the translation of evidence-based addiction prevention, treatment, and recovery interventions into routine practice, specifically focusing on non-addictive analgesic therapeutics.

Expired RFA-NS-24-019: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

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 Neurological Disorders and National Eye Institute ( NEI ) National Heart, Lung, and Blood Institute ( NHLBI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Dental and Craniofacial Research ( NIDCR ) National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) National Institute on Drug Abuse ( NIDA ) National Center for Complementary and Integrative Health ( NCCIH ) National Cancer Institute ( NCI ) Funding Opportunity Title HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional) UG3 / UH3 Exploratory/Developmental Phased Award Cooperative Agreement May 9, 2025 - Notice to Applicants That the Simplified Review Framework Will be Applied to All Relevant Applications for August/October 2025 Councils.

See Notice NOT-OD-25-116 . May 8, 2025 - Notice of Change: Expiration of RFA-NS-24-019: HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional). See Notice NOT-NS-25-024 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 04, 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 See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) 93. 853, 93. 273, 93.

121, 93. 866, 93. 865, 93.

313, 93. 846, 93. 867, 93.

847, 93. 395, 93. 838, 93.

837, 93. 839, 93. 840, 93.

233, 93. 213, 93. 279 Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to support preclinical optimization and development of safe, effective, and non-addictive small molecule and biologic therapeutics to treat pain.

The goal of the program is to accelerate the optimization and development of promising early therapeutic molecules and to facilitate readiness for the Early Phase Pain Investigation Clinical Network ( EPPIC-Net ) or other Phase II clinical studies.

Applicants must have a promising biologic or small molecule starting point for optimization, robust biological rationale for the intended approach, and identified assays for optimization of the agent.

The scope of this program includes optimization and early development activities, IND-enabling studies, development of a pharmacodynamic/target engagement biomarker, assembly and filing of an Investigational New Drug (IND) application and Phase I clinical testing.

This is a milestone-driven phased cooperative agreement program involving participation of NIH program staff in the development of the project plan and monitoring of research progress. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to receipt 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. No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

New Date May 8, 2025 per issuance of NOT-NS-25-024 . (Original Expiration January 08, 2027 ) 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 purpose of this notice of funding opportunity (NOFO) is to support preclinical optimization and development of safe, effective, and non-addictive analgesic small molecule and biologic therapeutics to treat pain.

The goal of the program is to accelerate the optimization and development of promising early therapeutic molecules and to facilitate readiness for the Early Phase Pain Investigation Clinical Network ( EPPIC-Net ) or other Phase II clinical studies.

Applicants must have a promising biologic or small molecule starting point for optimization, robust biological rationale for the intended approach, and identified assays for optimization of the agent.

The scope of this program includes optimization and early development activities, IND-enabling studies, pharmacodynamic/target engagement biomarker optimization and use, assembly and filing of an Investigational New Drug (IND) application, and Phase I clinical testing. The expectation is all projects will be entering first in human studies at the end of the project either through NIH contract or the grant.

This is a milestone-driven phased cooperative agreement program involving participation of NIH program staff in the development of the project plan and monitoring of research progress. This study is part of the NIH 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 the 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://www. nih.

gov/research-training/medical-research-initiatives/heal-initiative . More than 25 million Americans suffer from chronic pain, a highly debilitating medical condition that is complex and lacks effective treatments. In recent decades, there has been an over reliance on opioids for pain despite their poor ability to improve function.

This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative scientific solutions to develop alternative treatment options for pain are thus critically needed. As part of the mission of the HEAL Initiative, NINDS is working with other NIH Institutes and Centers to encourage the translation of basic research into new non-addictive pain treatments.

This program announcement is intended to create a foundation to initiate the optimization and development of pain therapeutics and catalyze the development of partnerships between the academic and industrial sectors so that translational research in pain can flourish as a cooperative, iterative process leading to safe, effective, and non-addictive treatments for pain.

Through this Notice of Funding Opportunity (NOFO), the NIH offers researchers funding for drug discovery and development activities that can be conducted in their own laboratories.

In addition, researchers have the opportunity to collaborate with NIH-funded consultants and contract research organizations (CROs) that specialize in medicinal chemistry and Good Manufacturing Practices (GMP) manufacturing, pharmacokinetics, biodistribution, protein and virus production, cell line and process development, QC release testing, toxicology, formulations development, and Phase I clinical studies.

The Program Director/Principal Investigator (PD/PI) will be responsible for conducting or leading all studies that involve disease- or target-specific assays, disease models, pharmacodynamic biomarkers and verification of the association between the therapeutic target or pathway and modulation by the therapeutic agent.

A PD/PI with, for example, medicinal chemistry expertise and resources, may request funding to conduct structure-activity relationship (SAR) studies in their own lab but collaborate with contractors on in vitro ADMET, in vivo PK, drug manufacturing and IND-enabling toxicology studies.

By contrast, a PD/PI with limited experience in drug discovery and development may opt to collaborate with NIH contractors for all activities not related to disease or target biology.

Applicants may propose to conduct all drug discovery and development activities themselves or collaborate with NIH contractors on activities of their choice, however, it is expected that all staff be in place at the start of the grant if not utilizing NIH resources for the work. For each project funded under this NOFO, the NIH will assemble a customized Lead Development Team (LDT).

The LDT will be co-chaired by the PD/PI and a NIH consultant and will include members of the PD/PI's team, additional subject matter expert consultants, and NIH staff. The LDT will establish an overall strategy for the project, plan studies to be conducted by NIH contractors, and coordinate activities across different research sites.

Potential applicants are strongly encouraged to contact NIH Scientific/Research staff and participating NIH Institutes/Centers prior to preparing an application to discuss how they may best utilize NIH contract resources and whether their application fits the mission of a particular NIH IC. See also Webinar information under Section IV. 7 below ("Other Submission Requirements and Information").

The NIH HEAL Initiative will require a high level of coordination and sharing between HEAL 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.

This program announcement is specifically focused on providing the expertise, resources and funding to expedite the preclinical translational development process necessary to advance small molecule and biologic non-addictive therapeutics for pain to Phase I clinical testing.

The program supports preclinical optimization and development of small molecules and biologics leading to the assembly and submission of an IND application and the implementation of Phase I clinical testing. The scope of this program excludes basic research, and projects focused on disease mechanism or mechanistic/mechanism of action studies of the intended therapeutic.

Further, development of animal models, diagnostics, rehabilitation strategies, or therapeutic devices is nonresponsive as are Phase II and Phase III clinical studies. Finally, this program is intended to provide support of the early therapeutic development process ; therefore, requests for support of only a single component of the process, such as a Phase I clinical trial or a GLP toxicology study are nonresponsive.

This is a two-phased program that is organized into a preparatory UG3 phase and an execution UH3 phase. Projects must enter at the UG3 phase of the program, and this phase must not exceed 2 years. Projects may enter the program at the Discovery or Development stage.

All projects must have the ultimate end goal of assembling an IND application and beginning a Phase I study by the end of the project. For entry at the Discovery Stage, projects must have a promising small molecule or biologic starting point for optimization, a rigorous biological rationale for the intended approach, and scientifically sound assays to test the agent.

Applications for entry at the Development stage must have identified the candidate therapeutic; no further optimization will be supported, including back-up programs. In addition, a strong package of data linking the putative therapeutic target to the proposed disease indication and supporting the hypothesis that altering the target activity will produce desirable outcomes for the disease is required.

Finally, the proposed therapeutic must have in vitro and in vivo biological activity and ADMET properties appropriate for the intended clinical use.

For the UG3 phase, this NOFO encourages projects proposing the following optimization activities: Optimization using potency and efficacy screens Preliminary efficacy testing in appropriate animal models for pain Characterization and testing for ADME (absorption, distribution, metabolism, and excretion) Initial development or optimization of pharmacodynamic/target engagement biomarkers associated with the therapeutic target or pathway Activities that fill in efficacy, in vitro non-GLP ADMET and in vivo PK gaps necessary to begin IND-enabling work It is expected that by the end of the UG3 phase, recipients will have characterized and selected lead candidates that are ready for in vivo efficacy testing, though additional optimization may be necessary.

Progression from the UG3 award to the UH3 award will be based on administrative review. After successful completion of the UG3 phase, a project may proceed to the UH3 phase.

For the UH3 phase, the following are examples of in-scope development activities: Any further optimization activities as listed above, if needed Non-GLP toxicology studies (e.g. dose range finding toxicology) Pharmacodynamic (PD) and related target engagement biomarker studies Formulation and stability studies Cell bank development and testing Gene expression level determination Biodistribution, tumorigenicity, and immunogenicity Manufacturing of candidate therapeutic for IND IND-enabling safety pharmacology, genotoxicity, hERG and toxicology studies IND assembly and submission It is expected that at the end of the UH3 phase, recipients will have advanced their therapeutic to Phase I clinical testing.

Applications Not Responsive to this NOFO Non-responsive applications will not be reviewed.

Applications will be considered nonresponsive of this announcement if they include: Screening to identify initial hit compounds Basic research and studies of disease mechanism Development of diagnostics and therapeutic or diagnostic devices Studies directed beyond Phase I clinical testing Opioid sparing projects and projects targeting the mu-opioid receptor Applications will be considered incomplete if they are missing any of the following: A target product profile (TPP) table Activities for both the UG3 (preparatory) and UH3 (execution) phases A budget for each year of the proposed project, including both UG3 and UH3 phases An Intellectual Property (IP) plan attachment Incomplete applications will be withdrawn .

See section IV for instructions for each of these elements. To support these projects, additional existing NIH resources may be made available to the applicant outside of this grant budget and are described below. Applicants are strongly encouraged to contact NIH staff to discuss these options.

These resources include, but are not limited to the following: NINDS has established contract support for medicinal chemistry (including synthesis/SAR, computational chemistry and in vitro ADMET), biodistribution, protein and virus production, antisense oligonucleotide production, antibody production, cell line process and development, cell banking, pharmacokinetic studies, toxicology (GLP and non-GLP) and safety testing, drug formulation and GMP manufacturing, QC release testing and Phase I clinical studies.

Contractors will provide data and reports in a format suitable for inclusion in an IND application. NIH also provides access to experts in therapeutics development through consulting contracts. Applicants must contact NINDS staff (contacts provided below) in order to utilize these resources and determine how to best leverage these as part of the application.

To learn more, visit the HEAL PTDP webpage: https://www. ninds. nih.

gov/current-research/trans-agency-activities/ninds-role-heal-initiative/pain-therapeutics-development-program-ptdp . As appropriate, applicants are encouraged to make use of the NINDS Common Data Elements ( https://www. commondataelements.

ninds. nih. gov/#page=Default ).

Pursuant to the development of analgesic medications without the liability of producing OUD following chronic use, the National Institute on Drug Abuse (NIDA) offers resources to conduct and support all phases of medications development. These programs include synthesis and preclinical evaluation of potential therapeutics, clinical trial design and execution, and preparing regulatory submissions.

More information can be found at: https://nida. nih. gov/about-nida/organization/divisions/division-therapeutics-medical-consequences-dtmc/research-programs#PDP The NIH HEAL Initiative supports the following resources outside this funding opportunity that are also focused on the development of safe, effective, and non-addictive therapeutics to treat pain.

Applicants that are interested in utilizing these complementary resources should contact PSPP or NCATS directly. PSPP: Within the NIH HEAL Initiative, NINDS created the Preclinical Screening Platform for Pain (PSPP) to identify and profile non-opioid, non-addictive therapeutics (small molecules, biologics, natural products, or devices) for pain. NIH staff assess the suitability of assets for acceptance into the PSPP on an ongoing basis.

Within PSPP, lead assets are profiled for efficacy in models relevant to human pain conditions. Program staff work with the asset owner to plan the evaluation and direct the studies, which are performed by a contract facility at no cost to the PSPP participants. All evaluation is done under a defined participant agreement that outlines confidentiality and intellectual property protection.

More information can be found at: https://heal. nih. gov/research/preclinical-translational/screening-platform Applicants are also encouraged to potentially develop collaborations with NIH National Center for Advancing Translational Sciences (NIH/NCATS) to access the state-of-the-art capabilities at the Center.

If selected for a collaboration, NCATS will make available capabilities in support of HEAL initiatives. The capabilities include, screening and scalable production of relevant stem cells and quantitative high-throughput screening to identify promising compounds to be optimized by medicinal chemists. A more detailed description of the capabilities can be found at: https://ncats.

nih. gov/heal/intramural-capabilities Because therapeutics optimization and development are inherently high risk, it is expected that there will be significant attrition as projects progress. Annual go/no-go milestones must outline achievements necessary for the project to progress through the stages of therapeutic development and be tailored to the specific therapeutic and its intended disease indication.

Proposed milestones will be used for measuring success in achieving each of the research plan key objectives. One or more milestone(s) must be used for each key objective. More details can be found in Section IV.

Application and Submission Information. Annual go/no-go milestones listed in the application will be finalized by a team consisting of the PD/PI and NIH program staff at the start of each project and updated as needed. If justified, future year milestones may be revised based on data and information obtained during the previous project period.

NIH program staff and leadership will conduct annual administrative reviews. At the end of the UG3 phase, NIH program staff and leadership will determine if the project will advance to the UH3 phase.

Annual and UH3 transition administrative reviews will be based on: Successful achievement of milestones The overall feasibility of project advancement, considering data that may not have been captured in the milestones Competitive landscape for the disease indication and drug target HEAL Programmatic priorities Since the ultimate goal of this program is to bring new pain therapeutics to the market, the creation and protection of appropriate intellectual property are significant considerations in designing research strategies and prioritizing projects for funding.

Each applicant is expected to address intellectual property issues (including permission to utilize proprietary reagents or materials if applicable) related to the proposed therapeutics, with input from the institution's technology transfer officials, if applicable. Peer reviewers will be instructed to comment on the intellectual property landscape for each application.

The project milestone plan may include commercialization milestones to protect and leverage intellectual property. Recipients of awards are encouraged to identify potential licensing and commercialization partners early in the therapy development process.

The PD(s)/PI(s) is encouraged to work closely with technology transfer officials at their institution, if applicable, to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner. See Section IV. 2.

Other Project Information for details. The program provides funding through the UG3/UH3 cooperative agreement mechanism. As a cooperative agreement, implementation will involve participation of NIH program staff in the planning and execution of the therapy-directed projects.

The UG3 portion of the award is designed to support optimization research for the first 1-2 years.

Based on the progress to milestones, only a limited number of projects will proceed to the UH3 phase for the remainder of the award period which will include final optimization and development leading to assembling an IND application and beginning a Phase I clinical study, either through the grant budget or through NIH contract resources outlined above.

IC-Specific Areas of Interest: NINDS is interested in the discovery and development of non-addictive therapeutics to treat pain disorders.

These disorders include, but are not limited to headache, migraine, post-stroke pain, neuropathic pain, pain following traumatic brain injury, pain associated with spinal cord injury, pain associated with Alzheimer’s disease and other dementias, pain associated with Parkinson’s Disease and chronic overlapping pain conditions. NINDS, as part of NIH, strives for rigor and transparency in all research it funds.

For this reason, NINDS explicitly emphasizes and provides supplemental guidance to NIH application instructions related to rigor and transparency ( https://grants. nih. gov/policy/reproducibility/guidance.

htm ). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, e.g., by minimizing the risk of bias and transparently reporting methods and results as described at https://www. ninds.

nih. gov/Funding/grant_policy . As stated in the NIH application guidelines, if previously published or preliminary studies do not meet these rigor standards to an acceptable degree, applicants should address how the current study design addresses the deficiencies.

Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity and transparency of experimental results.

NCCIH is interested in supporting neurotherapeutic research aimed at compounds and small molecules from natural products (e.g., cannabinoids, venoms, conotoxins, melatonin, microbial metabolites, etc.) that may be used or developed to modulate CNS-based symptoms with priority given to pain and pain related symptoms including sleep, stress, and mood disorders.

Investigators are strongly encouraged to discuss their research plans with the NCCIH Scientific/Research contact prior to submitting their applications. NIAAA is interested in developing novel non-addictive small molecules/biologicals to treat alcohol-associated pain conditions as well as treatment options for coexisting chronic pain and excessive alcohol use/AUD subjects.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is interested in supporting research aimed at developing novel, non-addictive pharmacotherapies for (1) more effective and safer treatment of pain in pediatric or obstetric populations; (2) the treatment of chronic gynecologic pain syndromes, including vulvodynia/vestibulodynia, chronic pelvic pain, dysmenorrhea, dyspareunia, and post-operative gynecologic pain; (3) the management of persistent pain in individuals with physical impairments and/or intellectual or developmental disabilities.

Investigators are strongly encouraged to discuss their research plans with NICHD Scientific/Research contact prior to submitting their application. The NIDDK encourages applications for research to develop therapies and technologies for pain conditions within the mission of NIDDK.

Topics of special interest include, but are not limited to the pain associated with diabetic neuropathy; urologic chronic pelvic pain syndromes such as Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) and Chronic Prostatitis/Chronic Pelvic Pain Syndrome; urinary stone disease and post-ureteroscopy stent-associated pain; functional gastrointestinal and motility disorders such as gastroparesis and irritable bowel syndrome; inflammatory bowel disease; hepatobiliary diseases such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and biliary dyskinesia; and exocrine pancreatic diseases such chronic pancreatitis.

NCI is interested in applications for research to develop non-addictive pharmacotherapies for cancer- or cancer-treatment related pain. Pain conditions of interest include, but are not limited to: bone cancer pain, oral cancer pain, metastasis-related pain, post-surgical pain, radiation pain (including skin), aromatase inhibitor-induced arthralgia, chemotherapy-induced peripheral neuropathy, and immunotherapy-related pain.

NEI is interested in applications that advance the understanding of, and potential therapy for, ocular pain. Ocular surface disease, and dry eye disease, present a currently unmet need despite clear clinical significance. Moreover, photorefractive surgery procedures can result in discomfort and pain in patients who undergo these procedures.

While most such patients report an eventual resolution of ocular pain symptoms some patients report longer-term chronic pain. The underlying biology that may account for such individual differences in outcomes is not well understood. NEI encourages applications under this NOFO that may advance non-addictive analgesic therapeutics development in this critical area.

Ultimately, the goal is to identify and validate novel or repositioned non-opioid analgesics for corneal pain. The NHLBI is interested in preclinical optimization and development of safe, effective, and non-addictive small molecule and biologic therapeutics for pain conditions within the mission of NHLBI.

Topics of special interest include, but are not limited to the pain associated with blood diseases such as sickle cell disease, hemophilia, and deep venous thrombosis and heart diseases and lung diseases such as chronic obstructive pulmonary disease, cystic fibrosis related arthritis, lung transplantation where opioid dependency can be an issue, chronic pain from tube thoracostomy, severe chronic cough, and pain associated with mechanical ventilation in critical care patients.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases.

In the context of this NOFO, NIAMS is interested in the development of novel non-addictive small molecules/biologicals for more effective and safer treatment of pain in rheumatological, orthopedic, dermatological, bone and cartilage, and muscle diseases.

The National Institute on Aging (NIA) encourages applications that optimize and develop novel, efficacious, and safe non-addictive small molecule and biologic therapeutics with relevance across a variety of pain conditions in the context of healthy aging as well as diseases and conditions associated with advancing age including multimorbidity and Alzheimer’s Disease and Related Dementias.

Important considerations for preclinical translational development include, but are not limited to, age-related changes in physiologic systems (e.g., renal, musculoskeletal, central nervous system) affecting drug metabolism and mechanisms of therapeutic action in the context of aging or aged organisms.

Given that the misuse of opioid analgesics can result in OUD, the National Institute on Drug Abuse (NIDA) is interested in evaluating new pain medications, irrespective of pain modality, with low or no risk of abuse in order to prevent the initiation of OUD. Similarly, NIDA is interested in those types of medications with the goal of reducing the progression to more severe forms of OUD.

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 for all across the continuum of research from basic through implementation studies.

The perspectives of other relevant collaborators (e.g., health service providers, payors, 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 for all, 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 ).

This NOFO will support applications that include a series of milestones for completion of the clinical trial and provide contingency plans to proactively confront potential delays or disturbances in attaining the milestones. Continuation of the award is conditional upon satisfactory progress, availability of funds, and scientific priorities of the HEAL Initiative.

If, at any time, recruitment falls significantly below the projected milestones for recruitment, NIH will consider ending support and negotiating an orderly phase-out of the award. NIH retains the option of periodic external peer review of progress. NIH program staff will closely monitor progress at all stages for milestones, accrual, and safety.

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 Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for this NOFO. Application Types Allowed 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. 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 NIH HEAL (Helping to End Addiction Long-term) Initiative intends to commit an estimated total of $11,000,000 to fund 4 awards 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 must reflect the actual needs of the proposed project but should not include the costs of NIH contract resources requested. The UG3 phase of the grant must be at least 1 year and cannot exceed 2 years. The UH3 phase cannot exceed 4 years.

The total duration may not exceed 5 years. The actual duration of individual projects will depend upon successful achievement of milestones and conditions as described in the Milestones and Implementation sections of the program overview. 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 All organizations administering an eligible parent award may apply for a supplement under this NOFO.

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) are not eligible to