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 Biomedical Imaging and Bioengineering (NIBIB)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Cancer Institute (NCI)
National Eye Institute (NEI)
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 Institute of Neurological Disorders and Stroke (NINDS)
National Center for Complementary and Integrative Health (NCCIH)

National Center for Advancing Translational Sciences (NCATS)

Funding Opportunity Title

HEAL Initiative: Translational Development of Devices to Treat Pain (U18 Clinical Trial Not Allowed)

Activity Code

U18 Research Demonstration – Cooperative Agreements

Announcement Type

New

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-EB-18-003

Companion Funding Opportunity

RFA-RM-19-001, U01 Research Project--Cooperative Agreements

RFA-NS-19-016, UG3/UH3 Exploratory/Developmental  Phased Award Cooperative Agreement

RFA-NS-19-017, U44 Small Business Innovation Research (SBIR) Cooperative Agreements - Phase II

RFA-NS-19-018, UH3 Exploratory/Developmental Cooperative Agreement Phase II

PAR-18-494, UG3/UH3 Exploratory/Developmental  Phased Award Cooperative Agreement

RFA-AR-19-028, UH2/UH3 Exploratory/Developmental  Phased Award Cooperative Agreement

Catalog of Federal Domestic Assistance (CFDA) Number(s)

 93.286; 93.273; 93,846; 93.393; 93.867; 93.865; 93.121; 93.847; 93.279; 93.853; 93.213; 93.350

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to support preclinical development and demonstration of safe, effective, and non-addictive device-based technologies and approaches to treat pain. The goal of the program is to demonstrate treatment using credible neural targets for device-based interventions and/or diagnostics for pain, building upon the latest mechanistic knowledge about the anatomy and physiology of central, spinal, and peripheral pathways involved in pain. Awarded activities will facilitate the translation of new devices up to the stage of readiness for first in human (FIH) clinical trials by overcoming key challenges identified during preliminary proof-of-concept studies. The scope of the program includes technology development and optimization, and studies to prepare for approvals for human use. This is a milestone-driven cooperative agreement program and will involve participation of NIH program staff in the development of the project plan and monitoring of research progress.     

Key Dates

 

Posted Date

December 10, 2018

Open Date (Earliest Submission Date)

January 8, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

March 22, 2019, June 20, 2019, October 22, 2019, February 21, 2020, June 22, 2020, October 21, 2020, February 22, 2021 , by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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.

AIDS Application Due Date(s)

 Not Applicable

Scientific Merit Review

April 2019, November 2019, March 2020, June 2020, November 2020, March 2021, June 2021

Advisory Council Review

May 2019, January 2020, May 2020, October 2020, January 2021, May 2021, October 2021

Earliest Start Date

July 2019, March 2020, July 2020, November 2020, March 2021, July 2021, November 2021

Expiration Date

February 23, 2021

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the 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.


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

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the 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

    Background:

    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.

    Scope:

    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.

    Additional Resources:

    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:

    SPARC

    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.

    BRAIN Initiative

    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.

    HEAL Initiative

    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.

    Milestones:

    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

    Intellectual Property

    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.)

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

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support 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 FOA.

    Application Types Allowed

    New
    Resubmission
    Revision

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    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

    Issuing IC and partner components intend to commit an estimated total of $3M to fund 5-10 awards in FY2019. Awards issued under this FOA are part of funds set aside to support the HEAL (Helping to End Addiction Long-term) initiative.

    Award Budget

    Application budgets are not limited but need to reflect the actual needs of the proposed project. Budgets should rarely exceed $500,000 direct cost per year.

    Award Project Period

     The scope of the proposed project should determine the project period. The maximum project period is three years of support.  

    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
    1. Eligible Applicants
    Eligible Organizations

    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:

  5. Hispanic-serving Institutions
  6. Historically Black Colleges and Universities (HBCUs)
  7. Tribally Controlled Colleges and Universities (TCCUs)
  8. Alaska Native and Native Hawaiian Serving Institutions
  9. Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
  10. 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

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

    • State Governments
    • County Governments
    • 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, including the NIH Intramural Program
    • U.S. Territory or Possession

    Other

    • 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
    • Regional Organizations
    • Non-domestic (non-U.S.) Entities (Foreign Institutions)
    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.

    Required Registrations

    Applicant Organizations

    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.

    2. Cost Sharing

    For grantees from a for-profit organization, this FOA does require cost sharing, as defined in the NIH Grants Policy Statement.  More information on cost matching requirements is in Section IV.2 R&R or Modular Budget

    3. Additional Information on Eligibility
    Number of Applications

    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.  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 NOT-OD-11-101).
    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 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.

    Letter of Intent

    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:

    Michael B. Wolfson
    National Institute of Biomedical Imaging and Bioengineering (NIBIB)
    Telephone: 301-451-4778
    Email: Michael.Wolfson@nih.gov

    Page Limitations

    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 FOA.

    SF424(R&R) Cover

    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 additional instructions:

    Other Attachments:

    IACUC Feedback. Applications are expected to use existing animal models, and will be required to submit IACUC approval prior to award.  Applicants may include an attachment that is no more than three pages entitled "IACUC Feedback.pdf", which contains communications between the PD/PI and the IACUC regarding use of the anticipated animal model. Ideally, these communications will describe the likelihood that the anticipated animal use protocol will be approved.

    Needs Assessment. Applications may include a needs assessment that is no more than three pages. Applications that exceed this limit will be withdrawn. This attachment should be entitled "Needs Assessment.pdf". The needs assessment should establish performance requirements with clear, quantifiable metrics and identify significant issues faced by stakeholders (patients, clinicians, caregivers, customers), which is a key step in the design control process and will be evaluated for adequacy.

    The Needs Assessment should:

    • provide strong, systematic evidence for the most efficient and effective route to addressing an unmet need;
    • critically evaluate primary or secondary data that have been used to identify deficiencies in current capabilities and the origins of the problem or critical barrier;
    • describe the beneficiaries of the proposed work and how their needs have been identified;
    • distinguish "wants" from "needs" and outline the involvement of those who will benefit in the development of a solution;
    • describe how finite resources can best be deployed to develop and disseminate a feasible and applicable solution; and
    • identify any human factors incorporated into the proposed research that optimize usability.

    Intellectual Property (IP) Strategy. Applications may include an IP strategy, no more than two pages long. Applications that exceed this limit will be withdrawn. 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.

    • Applicants should describe the IP landscape surrounding their device. Applicants should describe any known constraints that could impede their technology development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent protection and/or on the market, etc.) and how these issues could be addressed. 
    • If the applicant proposes using a component or method whose IP is not owned by the applicant's institution, the applicant should address any limitations imposed on the studies or the project (including IP generation) which would impede achieving the goals of the funding program, such as impeding robust licensing opportunities at project completion. Applicants should include a letter (see Letters of Support) from the entity that owns the IP indicating whether the entity will provide the technology, if there are any limits on the studies that can be performed with that technology, and agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.
    • If patents pertinent to the device being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, application status, and associated USPTO links, if applicable.
    • Applicants should discuss future IP filing plans. For a multiple-PD-PI and/or 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. 

    R&R Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.  In addition, the budget should include travel costs for the PD/PI to attend four meetings in the Bethesda, Maryland region.

    All instructions in the SF424 (R&R) Application Guide must be followed.
    Cost Matching Requirement for For-profit Applicants

    Cost matching or documented in-kind contributions is required for for-profit organizations responding to this FOA.  The for-profit awardee is required to match funds or provide at least a 50% matching of funds or documented in-kind contributions at a rate of not less than 50% of the for the total-Federally awarded amount (direct costs, as well as facilities and administrative costs), as stipulated by Public Law 115-141, the Consolidated Appropriations Act of 2018.   

    Federal funds may not be used as a source of matching funds. Generally, cost matching requirements may not be met from the following sources:
    a) Costs borne by another Federal grant or sub award;
    b) Costs or contributions toward cost sharing on another Federal grant, a Federal procurement contract, or any other award of Federal funds;
    c) Cost of services or property financed by income earned by contractors under a contract from the recipient (or sub recipient);
    (d) Program income; and
    (e) Patient incentives.

    The for-profit organization 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. Applicants must submit budgets that clearly document the total costs, the source and amount of matching funds, and how valuation was determined in the case of in-kind contributions, as well as the Federal and Institutional (non-Federal) components of the budget. 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.

    Budget Justification: All for-profit applicants must document the matching (non-Federal) component and the federal (non-matching) component in the total project budget. That is, the requested budget plus the cost-matching budget must be detailed in tabular format to document the cost-matching (non-Federal) component and the federal (non-cost matching) component. The amount of matching is subject to adjustment based on total allowable costs incurred.  All costs and contributions used to satisfy the matching requirement must be documented by the recipient, including how the value for in-kind contributions was determined, and are subject to audit. The cost matching requirement is not negotiable for for-profit organizations.

    R&R Subaward Budget

    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.  

    PHS 398 Research Plan

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: 

    Research Strategy

    The research strategy must focus on technology development rather than experimental or biological aims.  Applicants must describe the engineering design principles to be used to manage their projects.  These principles should specify how design requirements will be developed, refined, and validated; how risks and timelines will be managed; how milestones will be selected, tracked, and prioritized; how the team will be managed; and how resource allocations will be modified if obstacles are encountered during execution of the project. 

    While it is expected that the early- to mid-stage research supported by this FOA may not have fully been designed prior to submitting the application, applicants are nonetheless expected to provide initial target specifications that describe the intended capabilities of the device to be developed.

    Applicants must include a description of and justification for the specific pain condition(s) and population(s) being treated.  Applicants should compare their candidate device’s expected capabilities against the standard of care treatment for the pain condition(s) and population(s).  

    Applicants must justify the intended biological target/pathway and the technique to modulate neural activity. Applicants should provide evidence that this is a compelling target for the condition(s).  Supporting data may be preliminary (i.e., unpublished). Supporting data should adequately describe the rigor of those studies, and applicants could include details such as animal model, control groups, numbers in each group, steps used to eliminate potential bias, specific statistical analysis methods, the methodology used to validate the preliminary treatment, and the preliminary device used to perform preliminary studies. 

    Applications must propose milestones that represent verifiable go/no-go criteria for continued funding. The target specifications and attendant milestones are expected to be quantitative (e.g. “prototype survives 32 days under accelerated aging at 80 degrees C with less than 5% degradation in any one operational parameter”). Quantifiable (e.g. “we will measure how long it survives in accelerated aging”) or subjective (e.g. “our device will survive aging tests”) milestones and specifications are significantly less desirable. If a quantitative target specification or milestone is a “best guess estimate”, then applicants are encouraged to describe their assumptions and degree of confidence in the planned value. Applicants should furthermore provide a rationale for each criterion, such as a comparison against the state of the art.

    Details on methods, assumptions, experimental designs, and data analysis plans should be included for each milestone. Each milestone must have a timeline, and be incorporated into the overall project timeline, which should also be reflected in a Gantt chart. There should be at least one milestone proposed for completion at the end of each year. Ultimately, the milestones should be designed to provide confidence that the device will meet its target specifications, achieve a specific level of maturity at exit, and perform preclinical safety and effectiveness testing to inform at least one pre-submission meeting with the FDA.

    Experiments should be formulated to validate the technique or approach, and to demonstrate its capabilities, rather than advancing the state of biological knowledge.  Applicants must justify the specific techniques to be utilized for validation, and should relate them to the target condition(s) and population(s). Ensure the experimental design is rigorous. This includes, but is not limited to justification for model systems, endpoints, adequacy of controls and sample sizes, description of statistical analyses, inclusions of measures to reduce bias, and plans for replication, if applicable.

    A thorough risk analysis must be included.  It is expected that among the analyses, applicants will describe the maturity and limitations of existing components to be integrated into the device, the maturity and limitations of scientific knowledge about the biological mechanistic basis for the treatment, factors that may adversely affect the timeline, and factors that may limit translation into clinical use.  Applicants are encouraged to use a hazard analysis to inform the risk analysis.

    Although this FOA supports early- and mid-stage medical devices, applicants are nonetheless expected to consider barriers to translation, such as regulatory, reimbursement, IP, and commercialization factors. Applicants are expected to provide as much detail as possible. Applicants must describe the preliminary capabilities and maturity of any device or component to be integrated into the project and describe other resources, technologies, or capabilities to be incorporated into the system design. For each component to be developed within the project, applicants must justify why off-the-shelf components are inadequate. Applicants should also describe the anticipated plan after conclusion of the grant period, if successful.

    If any other NIH-provided resources will be utilized, these should be described.

    Any collaborators, consultants, or subcontractors should be identified, no matter when during the conduct of the research activity the proposed interaction occurs. Describe how the team, including consultants, has already been engaged and a plan as to how they will continue working together over the course of the project (e.g., recurring team meetings, review and report of data across disciplines, decision-making, participate in meetings with NIH, communication, etc.).

    If the applicant has any material from a preliminary needs assessment, it must be included in the separate Needs Assessment attachment as a part of your application package, and not in the Research Plan.

    Letters of support

    Letters should be included for all team members critical to the success of the project.  These letters should not be generic, but instead indicate what has been contributed so far and what they expect to provide during the project to allow an evaluation of team engagement.  

    • If applying from an academic institution, include a letter of support from the technology transfer official who will be managing intellectual property associated with this project.
    • If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
    • If collaborating with a private entity, include a letter of support that addresses any agreement to provide a device or technology, any limits on the studies that can be performed with said device or technology, any limitations on sharing of data (including negative results), and whether a licensing agreement(s) will be needed and in place once the project is funded. This letter should come from a high official within the private entity who has authority to speak on these issues.
    • If an application plans to utilize the infrastructure or resources of existing projects, whether funded by the NIH, other governmental or non-governmental entities, letters of support detailing the terms of collaboration, data sharing, and intellectual property must be included.

    For-profit applicants must include a letter(s) of support confirming that the required secured cost matching (cash; in-kind commitments such as salary, consultant costs, equipment) is available and confirm that the essential personnel have the authority within the organization to allocate resources. 

    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, with the following modification:

    Dissemination plans should include the following key elements:

    • Project management of resource sharing or dissemination;
    • Description of the specific resources to be shared;
    • Milestones with schedule for availability and for breadth of dissemination;
    • Persons who will have access to the resources (written as broadly as possible to the extent consistent with applicable laws, regulations, rules, and policies);
    • Plan for post award disposition of resources.  It is expected that preference will be given towards eventual commercial manufacture, although plans with an end-goal of future dissemination capitalizing on existing NIH or alternate funding agency funding mechanisms will be considered.
    • Applicants should anticipate that, if awarded, their project will join a consortium working group, coordinated by the NIH, to identify consensus standards of practice as well as supplemental opportunities to collect and provide data for ancillary studies, and to aggregate and standardize data for dissemination among the wider scientific community.  Accordingly, the Data Sharing Plan should include a statement of intention to join and cooperate with a future collaborative consortium of awardees to maximize data sharing opportunities (including collection, curation, analysis and sharing).
    • If patent protection is being sought, investigators should explain how data will be shared after filing for patent protection to allow for both further research and the development of commercial products to advance forward, consistent with achieving the goals of the program.

    Appendix:

    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 NIH-defined human subjects research, clinical research, and/or 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.

    Delayed Onset Study

    Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

    PHS Assignment Request Form

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

    Foreign Institutions

    Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions.

    3. Unique Entity Identifier and System for Award Management (SAM)

    See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

    4. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

    Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

    Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

    Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

    All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

    7. Other Submission Requirements and Information

    Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

    Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

    For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

    Important reminders:

    All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

    The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

    See more tips for avoiding common errors.

    Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

    It is strongly recommended that applicants consult with NIH program staff as plans for an application are being developed. Consultations will include email and, if needed, conference calls with NIH program staff. Early contact provides an opportunity for NIH program staff to discuss the program scope and goals, and to provide information and guidance on how to develop an appropriate milestone plan. Other aspects of an application that are unique to this program are also discussed.

    Applications Involving the NIH Intramural Research Program

    The requests by NIH intramural scientists will be limited to the incremental costs required for participation.   As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses.  Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. 

    If selected, appropriate funding will be provided by the NIH Intramural Program.  NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA.  Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights. 

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process.

    Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

    For this particular announcement, note the following:

    As proof-of-concept is required prior to entry, innovation will in part be evaluated by having a clear, comprehensive, and credible path towards transitioning an emerging technology to broad and routine clinical practice.

    The market size for the devices solicited in this FOA may be considered small compared to other markets. Provided these smaller markets are sustainable, applications should not be penalized for their comparatively smaller market. NIH is supportive of research for both rare and high incidence disorders that fall under the mission of NIH.

     
    Overall Impact

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

    Scored Review Criteria

    Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

    Further criteria specific to this opportunity: 1) How significant of an advantage will the candidate device offer over clinically available diagnostic, rehabilitative, or therapeutic approaches for the specified pain condition and population? 2) What is the strength of the rationale for the biological target?  3) Have the investigators considered the phenotype, physiology, and feasibility of treating the targeted clinical population in the design of their technology?   

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

    Further criteria specific to this opportunity:  1) Do the investigators have sufficient expertise in the target biology, pain condition, clinical phenotype, pre-clinical technology development, regulatory matters, technology translation, etc. in order to design, develop, and validate a diagnostic, rehabilitative, or therapeutic system? 2) Are the roles of each collaborator carefully defined in the research plan?  

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    Further criteria specific to this opportunity:  1) Would the device take a unique approach to target the relevant anatomy while limiting confounds or side effects? 2) Has the mechanistic basis of the biology been exploited for other clinically available pain treatments, or is it truly novel? 3) Does the application use state-of-the-art design practices to develop the device to the point of clinical testing? 4) Are the applicants making effective use of existing resources, technologies, and capabilities to speed translation?  

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

    Further criteria specific to this opportunity: 1) Is the overall plan for device development reasonable, including the plan after conclusion of the grant period? 2) Are design criteria informed by input from stakeholders and include clear and justifiable metrics for verification? 3) Is the regulatory plan reasonable in terms of the path to market and will it answer key questions about the appropriate regulatory standard (e.g., PMA, 510(k) de novo submissions)? 4) Are the experiments formulated to validate the technology and demonstrate safety and effectiveness for the specified pain condition(s) and population(s), rather than advancing the state of biological knowledge? 5) Have the applicants considered the critical factors that might limit clinical adoption?

    If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

    1) the protection of human subjects from research risks, and

    2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?  

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

    Further criteria specific to this opportunity: 1) Is there sufficient translational experience (e.g. regulatory, manufacturing, commercialization) to guide development of the device towards human use within five years? 

    Additional Review Criteria

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

     Milestones and Timelines
    • Are the milestones clear, quantitative, and representative of all of the critical steps in the progression towards translation? Will these milestones allow for unambiguous go/no-go decisions each year?
    • Will successful completion of these milestones provide confidence that the investigator will be able to successfully achieve the end goals within the timeline of this grant mechanism?
    • Are the timelines for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
    • Are there additional key steps or experiments that need to have milestones?   
    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

    For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

    Inclusion of Women, Minorities, and Individuals Across the Lifespan 

    When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

    Vertebrate Animals

    The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    Biohazards

    Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

    Resubmissions

    For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

    Renewals

    Not Applicable

    Revisions

    For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

    Additional Review Considerations

    As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

    Intellectual Property

    1) Does the application outline any known IP constraints that could impede technology development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent protection and/or on the market, etc.) and how these issues could be addressed while achieving the goals of this program? 2) Does the applicant outline the IP landscape of their technology? 3) If applicable, how strong is the applicant's IP portfolio/position (pertinent to the proposed project), and to what extent does the applicant have a reasonable strategy to protect its IP going forward? 4) If the applicant has filed patents pertinent to the technology, do they provide details about those patents? 5) If IP will be shared among co-investigators, does the applicant provide details about the plans for IP sharing? 6) Do the IP Strategy attachment and related letters of support address potential concerns?  

    Applications from Foreign Organizations

    Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

    Select Agent Research

    Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

    Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

    Specific to this FOA: How likely is it that the plans for cost matching will be adequate?

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

    As part of the scientific peer review, all applications:

    • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
    • Will receive a written critique.

    Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

    Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Biomedical Imaging and Bioengineering. The following will be considered in making funding decisions:

    • Scientific and technical merit of the proposed project as determined by scientific peer review.
    • Availability of funds.
    • Relevance of the proposed project to program priorities.
    3. Anticipated Announcement and Award Dates

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

    If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

    A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

    Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

    Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

    Special award condition specific to this FOA: A grantee from a for-profit organization funded under this 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.  See 45 CFR 75.306 for additional details.   Matching funds must be non-Federal funds set aside for this project and are available from the source(s) identified in the application, as committed to by the recipient. Cost matching will be evaluated by the awarding office to ensure that this requirement is being met. Compliance with the matching requirement must be verified on an annual basis and must be documented in the annual and final FFR.

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

    For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

    The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

    The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

    The PD(s)/PI(s) will have the primary responsibility for:

    • Defining the device design, prototype construction, experimental approaches, validation protocols, setting project milestones and conducting experiments.
    • Submitting quarterly progress reports during the funding period in a standard format, as agreed upon at the initiation.
    • Ensure that the data produced meets the quality standards and costs agreed upon at the time of award, or any improved quality standards and costs negotiated during the award period.
    • Participating as a non-voting member of the SPARC Steering Committee and joining relevant subcommittees, as described below under Areas of Joint Responsibility.
    • Adhering to applicable NIH Stimulating Peripheral Activity to Relieve Conditions (SPARC) Program policies, to be negotiated on a per-project basis with NIH.
    • Accepting and implementing any other common guidelines and procedures developed for the SPARC Program and approved by the NIH SPARC Steering Committee.
    • Accepting and participating in the cooperative nature of the coordinated NIH SPARC Program, which may include Consortium meetings.
    • Attending at least four workshops/meetings organized by the NIH during the award period. There will be an initial kick-off meeting and subsequent meetings at 6 month intervals in the Washington DC Metro region.  The PI and up to one other key personnel with complementary expertise are required to attend these meetings.  Funds to attend these workshops should be budgeted in the application.
    • Working closely with their institution's technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner. Awardees are responsible for pursuing patent protection and complying with NIH Intellectual Property policies.

    NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

    • A Program Officer will be assigned to each award. The Program Officer will be responsible for normal scientific and programmatic stewardship and guidance.
    • An NIH Project Team composed of NIH Program Staff of the ensuing awards as well as other Program staff of the HEAL, BRAIN, and SPARC ICs, will be created to ensure communication and continuity among the interested NIH ICs related to coordination among HEAL, BRAIN, and SPARC awards and with other activities funded by NIH.
    • The Project Team will include and be led by the Program Officer assigned to each award.
    • One or more extramural NIH program staff member will be assigned as the Project Scientist for each award. The same person may serve as the Project Scientist for multiple awards.
    • The Project Scientist(s) will also be members of the Project Team.
    • The Project Scientist(s) for an award will interact scientifically with the PDs/PIs and other named personnel of that award, as a partner in the research.
    • The Program Officer, the Project Scientist(s), and one other member of the Project Team will be members of the SPARC Steering Committee, as described below under Areas of Joint Responsibility.
    • The Project Scientist(s) interact scientifically with the SPARC Steering Committee, described below under Areas of Joint Responsibility, and may assist in research planning, may present experimental findings to the Steering group from published sources or from relevant awarded projects, may participate in the design of experiments agreed to by the Steering group, may participate in the analysis of results, and may help ensure that duplication is avoided.
    • Project Scientist(s) will assist in the development of a finalized project milestone plan at the outset of the project and approve the final milestone language for incorporation into the award notice.
    • Project Scientist(s), in consultation with the PIs, may suggest modification or additional experiments to be conducted prior to or during the award as an additional milestone(s). In most cases, these studies will be supported by additional funds from NIH.
    • The Program Officer and Project Scientist(s) will review and assess the scientific progress and compliance with SPARC Consortium guidelines and procedures through regular communications with the PD/PI, periodic site visits for discussion with awardee research teams, and/or other relevant methods. The Project Scientist(s) will make recommends regarding whether further funds should be released to the project.
    • In all cases, the role of NIH staff will be to assist and facilitate, but not to direct activities.
    • NIH leadership will make decisions on project continuation based on program staff recommendations, programmatic prioritizations and budget considerations. NIH program staff may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous year. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued.  In addition to milestones, the decision regarding continued funding will also be based on the overall feasibility of project advancement, considering data that may not have been captured in milestones, overall progress, NIH portfolio balance and program priorities, competitive landscape, and availability of funds.

    Areas of Joint Responsibility include:

    • A SPARC Steering Committee has been formed whose purpose is to transfer information between SPARC awardees in order to achieve the goals outlined in the overall SPARC program, and to establish publication, dispute resolution policies, and common protocols.
    • The SPARC Steering Committee is composed of PD/PIs (or the Contact PI in the case of multi-PI projects), Project Scientist(s), the Program Officer and one other member of the Project Team.

    Dispute Resolution:

    Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

    A final Research Performance Progress Report (F-RPPR), invention statement, and the expenditure data portion of the Federal Financial Report, including Federal and non-Federal share for cost matching, are required for closeout of an award, as described in the NIH Grants Policy Statement.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

    In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

    Section VII. Agency Contacts

    We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

    Application Submission Contacts

    eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

    Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

    General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Michael B. Wolfson
    National Institute of Biomedical Imaging and Bioengineering (NIBIB)
    Telephone: 301-451-4778
    Email: Michael.Wolfson@nih.gov

    Nick Langhals, PhD
    National Institute of Neurological Disorders and Stroke (NINDS)
    Telephone: 301-496-1447
    Email: Nick.Langhals@nih.gov

    Xincheng Zheng (Ted), M.D., Ph.D.
    National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
    Telephone: 301-594-4953
    Email: xincheng.zheng@nih.gov

    Merav Sabri, Ph.D.
    National Center for Complementary and Integrative Health (NCCIH)
    Telephone: 301-496-2583
    Email:merav.sabri@nih.gov

    Yolanda F. Vallejo, Ph.D.
    National Institute of Dental and Craniofacial Research (NIDCR)
    Telephone: 301-827-4655
    Email:  Yolanda.vallejo@nih.gov

    Houmam Araj
    National Eye Institute (NEI)
    Telephone: 301-451-2020
    Email: arajh@nei.nih.gov

    Diane St. Germain
    National Cancer Institute (NCI)
    Telephone: 240-276-7082
    Email: dstgermain@mail.nih.gov

    H. Joe Wang, Ph.D.
    National Institute on Alcohol Abuse and Alcoholism (NIAAA)
    Telephone: 301-451-0747
    Email: wangh4@mail.nih.gov

    Teresa Jones
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    Telephone: 301-435-2996
    Email: jonest@extra.niddk.nih.gov

    Theresa Hayes Cruz, PhD         
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-496-9233
    Email: cruzth@mail.nih.gov

    Danilo Tagle, Ph.D.
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-594-8064
    Email: Danilo.Tagle@nih.gov

    Peer Review Contact(s)

    Chief, Scientific Review Branch
    National Institute of Neurological Disorders and Stroke (NINDS)
    Telephone: 301-496-9223
    Email: nindsreview @mail.nih.gov

    Financial/Grants Management Contact(s)

    Pamela G. Fleming
    Chief Grants Management Officer, NIDA
    Telephone: (301) 480-1159
    Email: pfleming@nida.nih.gov

    Katie Ellis
    National Institute of Biomedical Imaging and Bioengineering (NIBIB)
    Telephone: 301-451-4791
    Email: kellis@mail.nih.gov

    Erik Edgerton
    National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
    Telephone: 301-594-7760
    Email: edgertont@mail.nih.gov

    Shelley Carow
    National Center for Complementary and Integrative Health (NCCIH)
    Telephone: 301-594-3788
    Email: carows@mail.nih.gov

    Diana Rutberg, MBA
    National Institute of Dental and Craniofacial Research (NIDCR)
    Telephone: 301-594-4798 
    Email: rutbergd@mail.nih.gov

    Karen Robinson Smith
    National Eye Institute (NEI)  
    Telephone: 301-451-2020 
    Email: Karen.Robinson.Smith@nei.nih.gov

    Amy Bartosch
    National Cancer Institute (NCI)
    Telephone: 240-276-6912
    Email: bartoschar@mail.nih.gov

    Judy Fox
    National Institute on Alcohol Abuse and Alcoholism (NIAAA)
    Telephone: 301-443-4704
    Email:  jfox@mail.nih.gov 

    Christina Coriz
    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
    Telephone: 301-594-8848
    Email: corizc@niddk.nih.gov

    Tijuanna Decoster
    National Institute of Neurological Disorders and Stroke (NINDS)
    Telephone: 301-496-9231
    Email: decostert@ninds.nih.gov

    Bryan Clark, MBA
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-435-6975
    Email: clarkb1@mail.nih.gov

    Jenelle Wiggins
    National Center for Advancing Translational Sciences (NCATS)
    Telephone: 301-435-0843
    Email: JWiggins@mail.nih.gov

    Section VIII. Other Information

    Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Authority and Regulations

    Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

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