This FOA is part of the NIH HEAL (Helping to End Addiction Long-term) Initiative—an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. The NIH HEAL Initiative will bolster 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://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.
Public Law 115-141, the Consolidated Appropriations Act of 2018 (signed March 23, 2018) includes a requirement that grantees from for-profit applicant organizations must provide a 50% match and/or in-kind contribution of all federally awarded dollars under the grant award (direct costs, as well as facilities and administrative costs) for research related to opioid addiction, development of opioid alternatives, pain management and addiction treatment.
Matching Requirement: A grantee from a for-profit organization funded under this funding opportunity announcement must match funds or provide documented in-kind contributions at a rate of not less than 50% of the total-Federally awarded amount, as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.The applicant will be required to demonstrate that matching funds and/or in-kind contributions are committed or available at the time of, and for the duration of, the award. Applications must identify the source and amount of funds proposed to meet the matching requirement and how the value for in-kind contributions was determined. All matching funds and/or in-kind contributions must be used for the portion of allowable project costs not paid by Federal funds under the grant award. NIH will not be the recipient, nor serve as a pass-through entity, of any such matching funds and/or in-kind contributions required under this announcement. See 45 CFR 75.306 for additional details.
An estimated 20.4% (50 million) Americans suffer from chronic pain and 8% (19.6 million) Americans suffer from high-impact chronic pain. This is a highly debilitating medical condition that is complex and lacks effective treatments. In recent decades, there has been an overreliance on opioids for chronic pain despite their poor ability to improve function. This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative solutions to develop alternative treatment options for pain are thus critically needed.
This opportunity is part of translational devices to treat pain, a coordinated set of initiatives within HEAL that are intended to support a device-based strategy for new non-addictive pain treatments. Although there are many devices available on the market to treat pain, their efficacy is limited by imprecise targeting resulting from insufficient mechanistic data about the ‘device-able’ targets, and from lack of closed-loop feedback to modulate the therapy. There is untapped potential to improve patient outcomes through new technologies with enhanced targeting and control. Other initiatives, referenced in the Companion FOAs section above, solicit grant applications to mechanistically research new targets and to demonstrate the viability of these “device-able” targets. Additional FOAs from the HEAL Initiative solicit applications to develop clinical-grade prototypes for new pain treatments, new preclinical models for pain, and discovery and validation of new biomarkers of pain.
As part of the mission of the HEAL Initiative, the participating NIH Institutes and Centers are encouraging the translation of early- and mid- stage technologies and approaches into new non-addictive pain treatments. This program announcement is intended to provide support for engineering activities to develop mature medical devices that are built upon a mechanistic understanding of the underlying biology. A secondary goal of this program announcement is to 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. This funding announcement is specifically focused on the preclinical translational development necessary to advance existing and emerging technologies and approaches to the point of clinical testing. The program supports bench and preclinical development of technologies and approaches leading to assembly of market approval applications for the FDA. The scope of this program excludes basic research, and studies of disease mechanism or mechanism of action studies of the intended device. Applications to this FOA should not be hypothesis-driven, but should propose design-directed development of a new technology or approach.
The intended use of candidate devices may be to diagnose, treat, or rehabilitate, and there are no restrictions on invasiveness (i.e., the devices may be non-invasive, minimally invasive, or invasive). The devices may be combination products involving use of drugs and biologic agents, however the drugs or biologics must already be approved by the FDA for use in pain treatment. Devices may utilize any viable modality to focally interact with the nervous system, such as optical, electrical, magnetic, acoustic, chemical/pharmaceutical, microfluidic, or combinations thereof. This FOA is not specific for any one or a group of pain conditions. Projects to treat novel targets for acute pain, chronic pain, migraine, other headache disorders, osteoarthritis, diabetic neuropathy, chemotherapy-induced neuropathy, sickle-cell pain, post stroke pain, etc. will be responsive. Projects to treat a combination of chronic overlapping pain conditions or for specific pathological conditions will be responsive. Projects that seek to treat novel targets in specific patient populations such as women and children will also be responsive to this FOA.
General Entry Criteria:
Projects must have a rigorous mechanistic biological rationale, and scientifically sound assays to test the device. Supporting data must be provided that the mechanism of therapy, rehabilitation, or diagnosis has been demonstrated in humans or bench top, ex vivo, in silico, in vitro, and/or in vivo models representative of the intended patient population and indication. Early stage technologies will be considered, as long as there is a sufficiently credible research plan and supporting data that clinical testing is likely to commence within five years.
It is expected that by the end of the project period, awardees will have validated the technology or approach in vivo and demonstrated a credible path towards transitioning an emerging technology to broad and routine clinical practice. Preclinical activities supported by this FOA are expected to generate preliminary safety and effectiveness evidence. If the target product is likely to be regulated by the FDA, this safety and effectiveness evidence should be provided to the FDA in a pre-submission meeting during the course of a supported project in order to determine the scope of research needed for a future pilot clinical study.
Successful applications must:
- Justify the anatomical target (e.g., nerve fiber or spinal circuit) to be affected or measured, and provide supporting data regarding the mechanism of the anticipated treatment. In addition, justification must be provided that the device will focally interact with the anatomical target.
- Identify and justify the specific pain condition(s) and population(s) to be addressed by the device, and describe the metrics to evaluate the effectiveness of the non-addictive treatment. If not using the standard of care metric for the specified pain condition(s), justify the metric to be used within the project.
- Have a clear plan to evaluate the progression and ultimate success of the project. Specifically, projects must have a clear timeline, quantitative benchmarks, milestones, and deliverables
- Use an existing animal model for the specific pain indication to be addressed by the device, unless no credible animal model exists. Applicants are not required to have tested a prototype device with this animal model, but IACUC approval for use of this animal model will be required prior to award. If IACUC approval cannot be provided in the application, applicants may provide feedback from their IACUC as an attachment, as described in Section IV.2.
- Describe the design practices that will be used to manage the project.
- Justify support for all resources and expertise (e.g. manufacturing partner, regulatory consultant, neuroanatomist).
- Justify the budget and duration of the project within context of the maturity upon entry, anticipated maturity upon exit, needed resources, and project risks, in addition to standard criteria.
Successful applications are expected to:
- Develop a technology or approach that is on a credible path towards clinical use within five years and commercialization within ten years, and perform a preliminary hazard analysis.
- Address the factors that lead to medical devices being considered a treatment of last resort, such as poor identification of responders, invasiveness, surgical revisions or complications, side effects, and unpredictable outcomes.
- Have a plan to continue developing the device after successful completion of the milestones. One example of such a pathway would be submission of an application to the companion HEAL Initiative FOAs to perform a clinical trial. Applicants are encouraged to consider the entry criteria and goals of these companion FOAs https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/funding-announcements-opportunities.
- “Begin with the end in mind,” using design-driven development principles, such as gathering input from stakeholders and manufacturing partners, and safe, consistent, and reliable operation. If the candidate device is considered to be very early stage, then applicants are expected to perform a needs assessment as a milestone. Otherwise the needs assessment is expected to be performed prior to grant application and be included in attachment, as described in Section IV.2.
- Leverage existing technologies and capabilities as much as practicable, working with SPARC and/or BRAIN PPP members or the pain screening program. Letters of support from all industrial partners are required, and signed agreements will be required prior to award. The SPARC and BRAIN PPP websites include template agreement documents.
- Consider, where appropriate, multi-PD/PI applications that integrate various domains of expertise, including engineering (biomedical, electrical, mechanical, industrial), computational (modeling, control theory, and statistical analysis), and scientific.
Applications will be considered non-responsive if:
- The project seeks to develop or validate animal models, diagnostic procedures, biomarkers, rehabilitation strategies, small molecules, or biologics. Applicants seeking to pursue these scopes of work are encouraged to consider other HEAL FOAs, available at https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/funding-announcements-opportunities.
- The primary objective is to study scientific or clinical hypotheses, efficacy, or effectiveness.
- The project does not conclude with clear path to human use.
- The basis for the device’s functionality is rooted in phenomenology or purely empirically determined measurements, and no credible mechanism of action is provided.
Applicants are strongly encouraged to consult the Scientific/Research Contact listed below to discuss the alignment of their proposed work with the goals of this FOA, and the HEAL Initiative.
To support these projects, additional existing NIH resources may be made available to the applicant outside of this grant budget. Applicants are strongly encouraged to contact NIH staff to discuss these options. These resources include, but are not limited to the following:
By constructing an open atlas of comprehensive anatomy and functional peripheral nerve connectivity with organs, SPARC teams are building the scientific foundation for the next generation of therapeutic closed-loop neuromodulation devices and protocols. Current SPARC projects can be browsed, by organ system, at the SPARC website, https://commonfund.nih.gov/sparc/fundedresearch. Applicants are encouraged to build upon the knowledge generated by these teams, and may contact SPARC investigators while preparing applications. Projects will be able to access resources from the SPARC consortium post-award.
The SPARC Program has also established Translational Partnerships https://commonfund.nih.gov/sparc/newmarkets, to facilitate partnership between mechanistic researchers and medical device manufacturers. Applicants to this FOA are also encouraged to contact the Translational Partners while preparing applications.
The BRAIN Initiative has established a Public-Private Partnership Program https://www.braininitiative.nih.gov/resources/brain_ppp/index.htm to facilitate partnerships between technology developers and medical device manufacturers. As with the SPARC Translational Partners, applicants to this FOA are encouraged to contact the PPP program participants while preparing applications.
The HEAL Initiative anticipates funding research to develop new “device-able targets” and to “engineer preclinical testing platforms to identify and profile non-addictive therapeutics for pain and addiction” through companion FOAs https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/funding-announcements-opportunities. Applicants are encouraged to collaborate with and build upon the knowledge gained within these initiatives.
In addition, the HEAL Initiative anticipates establishing support for a preclinical screening platform for pain and to make available a variety of in vivo animal models to test promising lead devices. 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.
Because technology development is inherently high risk, it is expected that there will be significant attrition as projects progress. Go/No-Go milestones will be established by a team consisting of the PD/PI and NIH program staff before the start of each project and updated as needed. These will be tailored to the technology to make sure that investigators have the appropriate resources to advance the proposed projects and will differ between projects. Program staff may consult as necessary with independent consultants with relevant expertise.
NIH program staff and leadership will conduct an annual administrative review. If needed, additional meetings to administratively review progress may take place. If justified, future year milestones may be revised based on data and information obtained during the previous project period. The 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 milestones
- Ongoing assessment of the competitive landscape for the technology or approach
- Program priorities
- Availability of funds
Since the ultimate goal of this program is to bring new pain technologies and approaches 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 encouraged to address intellectual property issues related to the proposed device, 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. If none is provided in the application, awardees will be encouraged to include commercialization milestones to protect and leverage intellectual property within the first year. Recipients of awards are encouraged to identify potential licensing and commercialization partners early in the development process. The PD(s)/PI(s) is encouraged to work closely with technology transfer officials at his or her 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.)
Deadlines: March 22, 2019, June 20, 2019, October 22, 2019, February 21, 2020, June 22, 2020, October 21, 2020, February 22, 2021 (letters of intent due 30 days prior to deadline)
Filed Under: Funding Opportunities