Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)
National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

National Cancer Institute (NCI)
National Eye Institute (NEI)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

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 Mental Health (NIMH)
National Institute of Nursing Research (NINR)
National Center for Complementary and Integrative Health (NCCIH)

National Center for Advancing Translational Sciences (NCATS)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.  The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women’s Health (ORWH)

Funding Opportunity Title
HEAL Initiative: Translational Devices to Treat Pain (UG3/UH3 Clinical Trial Optional)
Activity Code
UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement
Announcement Type
New
Related Notices
  • February 05, 2019 - Notice of Correction to Cooperative Agreement Terms and Conditions of Award for RFA-NS-19-020. See Notice NOT-NS-19-030.
Funding Opportunity Announcement (FOA) Number
RFA-NS-19-016
Companion Funding Opportunity

RFA-NS-19-017, U44Small Business Innovation Research (SBIR) Cooperative Agreement

RFA-NS-19-018, UH3 Exploratory Phased Award Cooperative Agreement

RFA-NS-18-041, R61/R33Exploratory/Developmental Phased Award

RFA-NS-18-046, ?R61/R33Exploratory/Developmental Phased Award

RFA-NS-18-042, R01Research Project Grant

RFA-NS-18-043, R21Exploratory/Developmental Grant

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

RFA-EB-18-003, U18 Research Demonstration – Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.350; 93.213; 93.393; 93.867; 93.273; 93.846; 93.853; 93.865; 93.279; 93.121; 93.847; 93.242; 93.361; 93.313; 93.286
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage investigators to pursue translational activities and clinical trials to treat pain with innovative, targeted, and non-addictive diagnostic and/or therapeutic devices that improve patient outcomes and decrease or eliminate the need to prescribe opioids. Activities supported in this program include implementation of clinical prototype devices, non-clinical safety and efficacy testing, design verification and validation activities, obtaining an Investigational Device Exemption (IDE) for a Significant Risk (SR) study or Institutional Review Board (IRB) approval for a Non-Significant Risk (NSR) study, as well as a subsequent small clinical trial (e.g., Early Feasibility Study). The clinical trial is expected to provide information about the device function or final design that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended 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.

This FOA will leverage Public-Private Partnership Programs (PPP) initiated under the NIH BRAIN Initiative, the Office of Strategic Coordination – The Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) Program, and the HEAL Initiative. These programs include agreements (Memoranda of Understanding,  MOU) with a number of device manufacturers willing to make such devices available, including devices and capabilities not yet market approved but appropriate for clinical research.  In general, it is expected that the devices' existing safety and utility data will be sufficient to enable new IRB NSR or FDA IDE approval without the need for significant additional non-clinical data. 

For more information see https://braininitiative.nih.gov/resources/brain_ppp/index.htmhttps://commonfund.nih.gov/sparc/newmarkets, and https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/public-private-partnership. Individuals, institutions, or businesses developing their own devices or that already have established collaborations with device manufacturers are welcome to apply directly to this FOA or the companion opportunities.

Key Dates

Posted Date

December 10, 2018

Open Date (Earliest Submission Date)
December 09, 2018
Letter of Intent Due Date(s)

30 days prior to receipt date

Application Due Date(s)
January 9, 2019, March 22, 2019, June 21, 2019, October 21, 2019, February 21, 2020, June 22, 2020, October 21, 2020, February 21, 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, June 2019, November 2019, March 2020, June 2020, November 2020, March 2021, June 2021

Advisory Council Review
May 2019, August 2019, January 2020, May 2020, August 2020, January 2021, May 2021, August 2021
Earliest Start Date

July 2019, October 2019, March 2020, July 2020, October 2020, March 2021, July 2021, October 2021

Expiration Date
February 23, 2021
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose:

The purpose of this Funding Opportunity Announcement (FOA) is to encourage investigators to pursue translational activities and clinical trials to treat pain with innovative, targeted, and non-addictive diagnostic and/or therapeutic devices that improve patient outcomes and decrease or eliminate the need to prescribe opioids. Activities supported in this program include implementation of clinical prototype devices, non-clinical safety and efficacy testing, design verification and validation activities, obtaining an Investigational Device Exemption (IDE) for a Significant Risk (SR) study or Institutional Review Board (IRB) approval for a Non-Significant Risk (NSR) study, as well as a subsequent small clinical trial (e.g., Early Feasibility Study). The clinical trial is expected to provide information about the device function or final design that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended 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.

Background:

This FOA is part of the NIH’s Helping to End Addiction Long-term (HEAL) Initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative 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. As part of the mission of the HEAL Initiative, NINDS is working with other NIH Institutes and Centers to encourage the translation of basic research into new non-addictive pain treatments. This program announcement is intended to encourage the translation of diagnostic and therapeutic devices to treat pain and catalyze the development of partnerships between the academic and industrial sectors so that translational research in pain can flourish as a cooperative, iterative process leading to safe, effective, and non-addictive treatments for pain.

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 applications to develop new neuromodulation technologies and to demonstrate the viability of new "device-able" targets. Additional FOAs from the HEAL and BRAIN Initiatives and the SPARC program 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 pre-clinical models for pain, and discovery and validation of new biomarkers of pain.

Objective:

The goal of this Funding Opportunity Announcement (FOA) is to translate innovative, effective, and non-addictive device-based technologies from pre-clinical studies to clinical trials to treat pain in humans. This FOA will support pre-clinical testing and clinical trials to answer key questions about the function or final design of a device.  Clinical trials supported are expected to provide information that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) and may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board (IRB), or Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the U.S. Food and Drug Administration (FDA), such as chronic implants. 

Overview:

Cooperative Agreements

This FOA utilizes a UG3/UH3 cooperative agreement mechanism to support non-clinical testing to enable IRB and/or an IDE approval necessary to conduct a small clinical trial, and the subsequent small clinical trial (e.g., Early Feasibility Study, see http://www.fda.gov/downloads/MedicalDevices/DeviceRegulati%20onandGuidance/GuidanceDocuments/UCM279103.pdf2  for details/definition).

All projects must have two phases; UG3 and UH3. The UG3 phase will support non-clinical testing toward obtaining of an IDE and IRB approval for an SR study, or to obtain IRB approval for an NSR clinical trial. All projects will start at the UG3 phase, and the length of UG3 phase will depend on the maturity of the project at entry and can range from one to four years. Only those UG3 projects that have met specific criteria (see below) will transition to the subsequent UH3 phase after NIH administrative review. The UH3 phase will support a small clinical trial and can last one to four years, however, the total project period (including both th e UG3 and UH3 phases) must not exceed five years.  Projects for which only a clinical phase is proposed should be submitted under the companion opportunity that utilizes the direct to UH3 activity code.

As a cooperative agreement, this FOA supports milestone-driven projects and involves NIH program staff's participation in developing the final project plan, monitoring the research progress, and making go/no-go decisions. NIH staff will also assist academic investigators in familiarizing themselves with the clinical device development process and the criteria needed to advance therapeutic leads and diagnostics to the clinic.  The expectations of the program are in line with those of industry regarding the advancement of devices through the translational developmental pipeline.  As such, an inherent rate of attrition is expected within this program.

Public Private Partnership Programs

This FOA for UG3/UH3 phased awards, along with the companion FOAs for U18 development, UH3 clinical research, and U44 SBIR applications, will leverage Public-Private Partnership Programs (PPPs) initiated through the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and the Office of Strategic Coordination – The Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) Program, which aim to facilitate partnerships between clinical investigators and manufacturers of latest-generation stimulating and/or recording devices to conduct clinical research for the treatment of pain.  Through these initiatives, the NIH is interested in reducing barriers to negotiating such partnerships and ensuring that new clinical trials leverage manufacturers' existing data. Data demonstrating safety and utility of these devices are very costly to obtain and pose a substantial barrier to research progress.

Types of research NIH plans to support with these partnerships include:

  • IRB-approved Non-Significant Risk (NSR) clinical research studies
  • New Significant Risk (SR) clinical trials requiring amendments to existing Investigational Devices Exemptions (IDEs) from the FDA 
  • SR clinical trials in which a new IDE would require no or minimal additional non-clinical testing
  • SR clinical trials in which a new IDE would require significant additional non-clinical testing, but leverages existing company device data.

The central feature of the PPPs is a set of template research agreements for collaborations between researchers, research institutions, and device manufacturers.  These template agreements were generated with substantial input from industry partners, clinical researchers, the FDA and representatives from institutional tech-transfer and contracts offices, and refined from input at a workshop held on June 3-4, 2015, (video of the workshop is publicly archived at http://braininitiative.nih.gov/meetings/June-2015-PPP.htm ) and a public feedback from a Request for Information issued in the NIH Guide (http://grants.nih.gov/grants/guide/notice-files/NOT-NS-15-032.html ).

There are three sets of agreement documents associated with the program, which are available at the following websites http://braininitiative.nih.gov/BRAIN_PPP/ and https://commonfund.nih.gov/sparc/newmarkets. 

Memoranda of Understanding (MOUs) agreed upon by NIH and device company partners to provide a framework under which the specified proprietary devices and associated support will be provided by these partners to HEAL awardees. 

Template Confidential Disclosure Agreements (CDA) to be signed by researchers to initiate detailed discussions that may require knowledge of proprietary company information relevant to the devices and proposed research.

Template Collaborative Research Agreements (CRA) to be used as common starting points for negotiations of agreements between the device manufacturer, researcher, and research institution. 

These template agreements have been developed to streamline interactions among the parties and expedite the formation of partnerships to conduct exploratory clinical research utilizing latest-generation devices for early-stage clinical research. The intent of the template agreements is to create a reasonable starting point for negotiations.  The NIH recognizes that specific terms and clauses may need to be altered for specific projects by consensus agreement of the two parties.   

Institutions or businesses that are developing their own devices are welcome to apply to  this FOA or any of the companion opportunities and are not limited to only working with companies participating in the BRAIN, SPARC, or HEAL PPP.  Likewise, companies that have already established formal collaborations with device manufacturers (that are part of either PPP or otherwise) are also allowed to apply.   

For applications proposing a collaboration with an industry partner, a successful application will be contingent on the applicant's ability to provide the NIH with documentation of company interest in allowing access to the selected device and associated data needed for conducting the proposed non-clinical trials and for filing an investigator-sponsored IDE or IRB NSR study in order to conduct the proposed exploratory clinical research study (e.g., an executed CRA or letter from the partner).  Final negotiations need not be completed at the time of submission, but an executed CRA will be required before issuance of grant award.

A list of devices being offered as part of the PPPs, along with associated information, can be found at https://www.braininitiative.nih.gov/resources/BRAIN_PPP/, https://commonfund.nih.gov/sparc/newmarkets, and https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/public-private-partnership.?

Scope:

Activities that can be supported in this program include implementation of clinical prototype devices, design verification and validation activities, demonstration of non-clinical safety and efficacy, pursuit of U.S. regulatory approval for a clinical trial, and conduct of a small clinical trial. The development and testing of both diagnostic and therapeutic devices of electrical, chemical, optical, sonic, or other relevant modalities that interface either invasively or non-invasively are within scope of this FOA. Therapeutic devices should address a specific, clinically meaningful purpose related to the treatment of pain. Relevant diagnostic devices should be novel tools used to characterize or identify the nature or cause of a medical condition. Existing diagnostic devices for which there is little to no development needed and the diagnosis serves as an endpoint and/or biomarker might also consider RFA-NS-18-041 or RFA-NS-18-046; Discovery of Biomarkers, Biomarker Signatures, and Endpoints for Pain and Analytical and/or Clinical Validation of a Candidate Biomarker for Pain, respectively.

As applicants must have comprehensive supporting data, including proof-of-concept demonstration with a near final prototype in a relevant animal model prior to entry, innovation will in part be judged on presenting a credible path towards an IDE or an NSR clinical trial.

It is expected that devices within the scope of this program either:

  • are very close to the 'final system' and manufactured using very close to the same manufacturing process as the device to be marketed or studied in a larger clinical trial following the completion of this project; or
  • require early feasibility clinical data to inform the final device design or manufacturing processes.

Entry Criteria

For entry to the program, projects should have:

  • Comprehensive supporting data based on bench, in vitro, and/or in vivo models representative of the intended patient population and indication.
  • Identified one or more clinically meaningful device outcome measures based on input from both clinicians and patients, as well as supporting literature.
  • A compelling case for obtaining IDE and IRB approvals for a SR clinical trial, or IRB approval for an NSR study prior to starting the UH3 phase.
  • Applicants are encouraged, but not required, to consult with FDA via a Pre-Submission meeting, study risk designation request, and/or 513(g) submission prior to applying for funding through this grant mechanism. Applicants who do not have sufficiently relevant feedback from the FDA regarding all planned activities prior to application for funding will be expected to do so as the first milestone during the first year of the UG3 phase of the award (see https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/NeurologicalDevices/default.htm and https://www.youtube.com/watch?v=u0zPKPLW2mU for helpful resources). Funding will be restricted to a maximum of $100,000 in direct costs until FDA feedback that is consistent with the likely success of the regulatory path to market and overall device development plan outlined in the grant application is received. In the event that FDA feedback is not consistent with the plans in the grant, program staff will evaluate the concerns and change of scope that would be needed and work with the investigators to determine the most appropriate course of action. Project plans and timelines should plan accordingly for these first activities of the award.

 

UG3 Phase Scope

Examples of studies that may be proposed during the UG3 phase include, but are not limited to:

  • Non-Good Laboratory Practice (GLP) animal studies to develop surgical techniques relevant to the device, optimize relevant therapeutic parameters, and refine device design as necessary for subsequent GLP testing or additional clinical trials for regulatory approval.
  • Bench-top and animal testing to demonstrate compliance with FDA Recognized Standards.
  • GLP compliant large animal model safety and/or testing of an implanted device.
  • Activities to become current Good Manufacturing Practice (GMP) compliant.
  • Activities to bring the development process under Design and Quality Systems Control,
  • Device, software, and firmware design verification and validation activities.
  • Development of packaging, connectors, and other accessories necessary for the translation of this technology.
  • Regulatory activities, including pre-submission meetings with FDA, IDE submission, or other FDA regulatory submissions (e.g., Humanitarian Use Device (HUD) Designation, Request for Risk Designation, 513(g) submission).
  • A limited clinical experience is also allowable during the UG3 phase if it is necessary to support the IDE submission for the small clinical trial conducted in the UH3 phase. Clinical trials in the UG3 phase are out of scope if the planned UH3 phase small clinical trial is NSR.

UH3 Phase Scope

The UH3 phase will support a small clinical trial that will lead to either:

  • a marketing application if only a small clinical trial or experience is needed to demonstrate the device is safe and effective;
  • a larger clinical trial that will lead to a marketing application; or
  • use of the clinical experience to inform device design decisions.

Examples of studies that can be proposed during the clinical phase include, but are not limited to:

  • Optimization of the device design with respect to the human functional anatomy;
  • Identification of the most simple, reliable, and cost-effective device configuration for more advanced clinical trials and eventual market approval;
  • Basic proof-of-concept testing in human patients;
  • Studies of the key physiological variables that may impact the function of the device in humans; or
  • Initial assessments of device safety are expected, but only in conjunction with obtaining enabling data about device design or function.

The following activities are non-responsive to this FOA, and will not be reviewed:

  • animal model development: all in vivo models must be well established and characterized, and available to the applicant;
  • efforts to develop neurotechnology for study of the fundamental function or physiology;
  • delayed-onset studies; and
  • projects focused augmentation of neural function in healthy individuals.

Milestones

Because device development is inherently high-risk, attrition is anticipated as projects move through the process. To help mitigate this risk, applications must propose one or more milestones associated with each of the research plan's objectives, in each year of the project. Milestones are goals that measure success and/or efficacy that can be used for go/no-go decision-making for the project and should have quantitative success criteria and the rationale for that criteria associated with them (see Section IV.2 for details). Quantitative criteria should be robust and consistent with the state-of-the-art in the field. ?Details on methods, assumptions, experimental designs, and data analysis plans (if the results are quantitatively measured) 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.

NIH program staff will contact the applicant to discuss and negotiate the proposed milestones and any changes suggested prior to funding the application. The final agreed upon and approved milestones will be specified in the Notice of Award (NoA). Progress towards achievement of the final set of milestones will be evaluated by NIH program staff on a yearly basis. Program staff may involve independent consultants with relevant expertise. If, based on the progress report, a funded project does not meet the yearly milestones, funding for the project will be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, portfolio balance and program priorities, competitive landscape, and availability of funds.

NIH encourages increasing the rigor and reproducibility of observed results. In some cases, conducting additional critical experiments will be important for NIH to have confidence in making a funding decision. Therefore, program staff may suggest modification or additional experiments that need 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.

UG3 phase to UH3 phase transition:

An administrative review will be conducted by program staff, with potential input by independent consultants, to decide whether a UG3 phase project will transition into the UH3 phase based on the

  • successful achievement of the defined milestones for the UG3 phase of the project;
  • likelihood of success in clinical testing;
  • competitive landscape;
  • program balance;
  • availability of funds;
  • for significant risk studies, an approved IDE for the clinical trial from the FDA;
  • IRB approval(s);
  • submission of the final clinical protocol and supporting documents to NIH for administrative review, and notification of approval by NIH;
  • feedback on activities involving humans subjects obtained from the Safety and Risk Assessment Committee (SARAC); and
  • agreement on updated timeline, milestones and budget for the clinical trial.

Quality and Compliance Requirements

The use of the Design Control and Quality Systems processes (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm070627.htm ) to the degree specified by the FDA is required. Intermediate steps in the Design Control process (e.g., design reviews, design verification, design validation, and design transfer activities) where appropriate, and IDE submission should be represented in the annual milestones. NIH recognizes that the degree to which Design Controls and Quality Systems processes are required by the FDA may vary substantially depending on the specific device. Investigators are encouraged to discuss these issues with the FDA and regulatory consultants prior to submitting an application so the extent to which these processes are required is clearly defined and verifiable in the application. Applicants should consider the Quality System requirements at the IDE stage (i.e., design controls) when preparing their device development activities. Applicants should consider Guidelines and Policies for Monitoring Clinical Research in the formation of a plan for data and safety monitoring as required by the appropriate IC.

Intellectual Property (IP)

Since the ultimate goal of this program is to bring new therapeutic and diagnostic devices to the market, the program strongly encourages the awardees and/or their collaborators to obtain and retain any IP developed around the device during the project period (see instructions on attachment or letters to address IP issues in Section IV). Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the device development process. The PD/PI(s) are expected to work closely with technology transfer officials at their institution to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. For rare or ultra- rare diseases where commercialization may be challenging, applicants are encouraged to discuss alternative strategies with Scientific/Research staff to get further guidance.

Pre-Submission Consultation

As a cooperative agreement, implementation will involve the participation of NIH program staff in the planning and execution of the projects.  Applicants are strongly encouraged to consult with NIH Scientific/Research staff when planning an application. Early contact provides an opportunity for NIH scientific/research staff to provide guidance on program scope, goals, and appropriate yearly milestones with metric driven criteria that can be verified by NIH staff for sufficiency. Applicants should contact NIH Scientific/Research staff as early as possible before a due date.

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?
Optional: Accepting applications that either propose or do not propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

Issuing IC and partner components intend to commit an estimated total of $4M to fund 3-6 awards.

Award Budget
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period
The duration of the UG3 phase cannot exceed 4 years and the total duration of the UG3/UH3 phases combined may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

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:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • 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

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply


Non-domestic (non-U.S.) components of U.S. Organizations are not 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) (formerly CCR) – 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.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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

 

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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:

Nick Langhals, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Fax: 301-480-1080
Email: nick.langhals@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.

Needs Assessment: Applications must 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 human interaction, productivity, and understanding while using the technology.

Intellectual Property (IP) Strategy: Applications are expected to include an IP strategy that is no more than three pages. Applications that exceed this limit will be withdrawn. This attachment should be entitled "IP Strategy.pdf" which will be reflected in the final image. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

 

A goal of this program initiative is to advance research towards the development of products that will benefit the public. Accordingly, applicants should describe the IP landscape surrounding their therapeutic or diagnostic device. This should include any known constraints that could impede the development of their therapeutic device or diagnostic (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent and/or on the market, etc.) and how these issues could be addressed as appropriate and consistent with achieving the goals of the program. If the applicant proposes using a device or technology whose IP is not owned by the applicant's institution, either an investigational therapeutic or diagnostic, FDA-approved therapeutic or diagnostic, or other licensed product, the applicant should address any questions that may constrain or impede its ability to operate and move the technology forward consistent with achieving the goals of the program. Applicants should include a letter (see Letters of Support) from the entity that owns the IP indicating whether the entity will provide the device or technology, if there are any limits on the studies that can be performed with that device or 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 therapeutic or diagnostic device being developed under this application have been filed, the applicants should indicate the details of filing dates, what types of patents are filed, application status, and associated United States Patent Office (USPTO) links, if applicable. 

 

Applicants should also discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe how IP will be shared or otherwise managed, and the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions in the Team Management Plan.

Communications with the IRB: For projects requiring non-clinical testing to support an IRB NSR designation, preliminary communications (e.g., letter or other documentation) with the IRB indicating what non-clinical testing will be necessary to support the NSR clinical trial should be included with a description of how the feedback will be incorporated. This attachment should be entitled "IRB_Communications.pdf" which will be reflected in the final image

SF424(R&R) Senior/Key Person Profile
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.

The budget should include funds necessary for travel for up to two key personnel to participate in a consortium meeting in the Washington D.C. area for each year of the project.

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:

Specific Aims: 

In the single Specific Aims attachment, include aims delineated for the non-clinical testing and the clinical trial.

  • Define the aims of the UG3 phase non-clinical development of the device.

  • Define the aims of the UH3 phase clinical trial.
  • A scientific hypothesis is not required nor expected for work of this nature.

Research Strategy: 

The single Research Strategy attachment should include the following subsections:

Significance

Clinical Impact and Feasibility

The target patient population and intended use should guide the design of the device and of the pre-clinical studies.

  • Describe the current state of knowledge of the etiology, clinical characteristics, and current and projected prevalence of the proposed disease indication.
  • Briefly discuss available treatments, their limitations, and how the proposed project would address an unmet clinical need or provide a benefit over existing therapies, regardless of therapeutic class (i.e. agents and devices).
  • Identify one or more clinically robust and meaningful device outcome measures based on input from both clinicians and patients, and supporting literature.
  • Discuss how the proposed project would affect clinical practice and how it relates to therapy development efforts underway in academia and industry, including both agents and devices.

Supporting Data for Entry

  • Include comprehensive data and information that validate the feasibility of conducting studies to address the specific aims.
  • When presenting results, sufficient information must be available about study design, execution, analysis, and interpretation.
  • PD(s)/PI(s) should explain the choice of models or assays, primary, secondary and exploratory endpoints and how they are clinically relevant.
  • Proof-of-concept data of device function are required prior to submission.  These data must be obtained using a prototype device close to the final device design anticipated for clinical testing, ideally tested in an in vivo animal model representative of the intended patient population.  Consequently, the supporting data for entry should include a description of the device with sufficient detail for reviewers to assess if the device used to obtain proof-of-concept data is representative of the final device design proposed for accelerated non-clinical testing to enable the proposed clinical studies.
  • As applicants must have comprehensive supporting data, including proof-of-concept demonstration with a near final prototype - prior to entry, innovation will in part be judged on presenting a credible path towards an IDE or an NSR clinical trial.

Approach

Overall Device Development Plan ?

Applicants must include an overall plan for device development. This plan should include:

  • A clearly stated device development timeline that includes practical, achievable goals leading up to, during, and beyond the proposed clinical trial.
  • Discussion of how feedback from appropriate U.S. regulatory bodies (e.g., FDA in the form of pre-submission meetings and IDE submission) has been incorporated into the development plan, if available.
  • Clinical considerations including, but not limited to, the tools and process for device insertion and method for evaluating the functional integrity of the device. This plan will often involve collaboration between the investigators, clinical researchers, and may include the participation of private-sector companies and/or voluntary agencies.

Detailed Plans for Research Strategy

In this section applicants should elaborate on their device testing strategy to enable the clinical studies. Research plans and milestones for the clinical trial (UH3 phase) should be included in the PHS Human Subjects and Clinical Trials Information forms.

  • UG3 Phase:
    • A project plan compatible with an accelerated timeline to obtain approval to conduct the clinical trial.
    • A clearly stated device testing timeline that includes quantifiable, practical, achievable goals in support of the proposed clinical trial.
    • A description of all non-clinical testing necessary to support the filing of an IDE or to obtain IRB approval for an NSR clinical trial, including the standards to which the testing will comply (e.g., Good Laboratory Practices (GLP), International Organization for Standardization (ISO) 11135, ISO 10993, electromagnetic Compatibility (EMC), International Electrotechnical Commission (IEC), etc.).
    • Plans for contact with and submissions to the appropriate U.S. regulatory bodies (e.g., FDA in the form of pre-submission meetings and IDE submission), if applicable.
    • Plans for all necessary animal studies required by the FDA to support an IDE. Large animal safety studies (e.g., canine, porcine, ovine, etc.) are often required by the FDA and should be considered in this section. Applicants should include a large animal GLP safety study conducted on the full-final device system using the final manufacturing process intended to support the IDE. If a large animal safety study is not required by the FDA for an IDE, or a test of the full final system using final design and manufacturing processes is not required, applicants should note this in this section and include a communication from the FDA clearly stating this is the case in the form of a response to a Pre-Submission via the "Communication with Regulatory Bodies" attachment ( PHS Human Subjects and Clinical Trial Information, Section 4.6a, Attachment 1, see below).
    • Anticipated risks in the device testing process, including potential needs for design changes, and mitigations based on initial test results.
    • A description of any independent contractors and their role(s) in the proposed non-clinical study.
    • A description of oversight groups that may be formed and their role(s) in the proposed study.
    • Only minor alterations to the device design necessary to enable the anticipated clinical trial.
    • Appropriately timed device design modifications to avoid impacting the validity or schedule for the proposed non-clinical testing.
    • A clear indication that study conceptualization and planning are at a stage sufficient to allow for an assessment of the likelihood of clinical trial success.
    • No clinical dependencies on the development of new and previously untested device elements/concepts that have significant risk of failure
    • Applicants are strongly encouraged to hold a pre-submission meeting with the FDA to discuss the clinical trial protocol prior to submission of an IDE, as described above. If the stated goal of the small clinical trial is to obtain data to support a marketing application, then a clear non-binding indication that the proposed clinical trial protocol is likely sufficient for that purpose must be obtained during this pre-submission meeting.
  • UH3 Phase:
    • Elaborate on the device testing strategy to enable the clinical studies
    • I nvestigators should clearly articulate what the next step will be in device development assuming a successful outcome of the clinical trial
    • Justify the outcome metrics for the proposed clinical trial in terms of quantifiable minimum-success criteria necessary to enable this next step.
    • Research plans and milestones for the clinical trial should be included in the PHS Human Subjects and Clinical Trials Information forms.
  • Milestones and Timeline:

Applicants are required to provide detailed Milestone Plan with project performance and timeline objectives. These milestones will be negotiated prior to issuing the notice of award.

  • UG3 Phase Milestones:
    • UG3 milestones that focus on those tests that are needed to obtain an FDA IDE or an IRB NSR designation. This may include but is not limited to bio-compatibility testing and large animal studies.
    • For projects proposing non-clinical testing to support an IDE submission for the clinical trial, at a minimum, an FDA pre-submission meeting, with NIH program staff in attendance, is required as a Year 1 milestone. If the need for additional pre-submission meetings is anticipated, they should also include NIH program staff and should be included as milestones. Non-binding FDA feedback during and after this meeting must clearly indicate that the proposed non-clinical testing plan is sufficient to support a successful FDA submission for an IDE by the end of the non-clinical UG3 phase. For projects requiring non-clinical testing to support an IRB NSR designation, preliminary communications (e.g., letter or other documentation) with the IRB indicating what non-clinical testing will be necessary to support the NSR clinical trial should be included as a Year 1 milestone. The milestone plan should be constructed so that FDA and/or IRB feedback on the testing plan can be incorporated into the design of critical tests prior to their initiation.
    • A project timeline in the form of a Gantt chart that includes all milestones described in the text should be included.
  • UH3 Phase Milestones:
    • Milestones and timeline related to human subjects and clinical trials related to the UH3 Phase should be included in the PHS Human Subjects and Clinical Trials Information form, Section 2.

Letters of Support

Applicants should include a letter of support from consultants, contractors, and collaborators.

  • If applying from an academic institution, include a letter of support from the technology transfer official who will be managing IP associated with this project.
  • If research will be performed at more than one institution, include a letter of support from each institution clarifying how IP will be shared or otherwise managed across the institutions as appropriate and consistent with achieving the goals of the program.
  • If collaborating with a private entity, state if they are agreeing to provide the device (or technology), whether there are any limits on the studies that can be performed with that device (or technology) or limitations on sharing of data, and whether licensing agreements are in place.

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Investigators are expected to include a brief one-paragraph description of how the final research data will be shared or why data-sharing is not possible.
  • 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.
  • Applicants should anticipate that, if awarded, their project will join a consortium work 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) for this unique population of human subjects.

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 with the following additional instructions:

Section 2 - Study Population Characteristics

2.7 Study Timeline

UH3 Milestone Plan

Applicants are required to provide detailed project performance and timeline objectives (note, UG3 milestones should be included in the Research Strategy section of the application). These milestones will be negotiated prior to issuing the notice of award. Applications that lack a Milestone Plan are considered incomplete and will not be peer reviewed.

Applicants should include a timeline and quantitative milestones for completion of key stages of the trial, especially participant recruitment, enrollment, and retention through the planned follow-up periods.

Yearly minimum success criteria for ongoing evaluations of device safety and efficacy that define clear go/no-go points should also be included as milestones.

A project timeline in the form of a Gantt chart that includes all milestones described in the text should be included

 

Examples of appropriate topics covered by UH3 Milestones include:

  • Finalization of clinical protocol (with program agreement, if applicable);
  • Registration of clinical trial in ClinicalTrials.gov;
  • Completion of regulatory approvals;
  • Enrollment of the first subject;
  • Enrollment and randomization, if applicable of the projected study population, including women, minorities and children (as appropriate);
  • Completion of data collection time period;
  • Completion of primary endpoint and secondary endpoint data analyses;
  • Completion of final study report;
  • Reporting of results in ClinicalTrials.gov;
  • Other protocol-specific performance milestones and timeline; these milestones will be negotiated prior to issuing the award, if appropriate.

 

Section 3 - Protection and Monitoring Plans

3.5 Overall structure of the Study Team

Team Management Plan

The team management plan must not exceed two pages. Applications that exceed this limit will be withdrawn. NIH strongly encourages applicants to form multidisciplinary teams that consist of non-clinical and clinical scientists, disease experts, regulatory experts, experts in manufacturing under Quality Systems and Design Controls, and other relevant academic/industry experts. This multi-disciplinary team should be able to define the overall device development plan to ensure gaps that need to be filled can clearly be defined and addressed during this funding period, to design the details of the plans and experiments, and to execute the research strategy. An organizational structure that clearly defines the team structure and relationships among the various components must be described in the team management plan and illustrated in an organizational chart. This plan should also describe the governance and organizational structure of the leadership team and the research project, including communication plans, processes for making decisions on scientific direction, intellectual property, and procedures for resolving conflicts. For publications, policies to address the ordering and recognition of authors, and decisions about what material to publish, consistent with the interests of commercial partners (where applicable), should be presented.

The team management plan must establish and name a Scientific Steering Group (SSG) that consists of senior and/or key team members and meets regularly to discuss project status, problems, and directions. In cases of partnering organizations/institutions, the SSG should include representatives from each organization/institution. Those individuals identified in the team management plan, who together would have the intellectual and leadership responsibilities, would likely be members of the SSG. Technology transfer officials from the participating organizations are also encouraged to be members of the SSG. Plans for enhancing the abilities and opportunities for investigators to work across disciplinary boundaries should also be included.

Section 4 - Protocol Synopsis
 
4.6 Will the study use an FDA-regulated intervention?
 
4.6.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status:
 
Communications with FDA:

  • Applicants should include minutes from all pre-submission meetings, notice of IDE, risk determination, email communications, and other relevant documentation. This material should only be submitted in section 4.6.a of the application or as post-submission material.  
  • Large animal safety studies are often required by the FDA to support an IDE. Applicants should include a large animal GLP safety study conducted on the full-final device system using the final manufacturing process intended to support the IDE. If a large animal safety study is not required by the FDA for an IDE, or a test of the full final system using final design and manufacturing processes is not required, applicants should include a communication from the FDA clearly stating this is the case in the form of a response to a Pre-Submission. If these studies are proposed, but ultimately not needed, program staff will work with the investigators to remove the relevant milestones and associated costs of these activities from the award.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Long Term Plan for Patients

The Long Term Plan for Patients must not exceed three pages. Applications that exceed this limit will be withdrawn. This attachment should be entitled "Long Term Plan for Patients.pdf" appended with 1, 2, 3, etc., as needed. Applicants must describe a plan for the care of patients at the end of the study and after the study period, if appropriate. These plans may vary from project to project; examples might include 1) explant of indwelling devices once the approved study period is complete, 2) surgical removal of batteries and 'capping' the exposed metals from leads/IS-1 connectors, 3) manufacturer-supported device maintenance for patients responding to therapy, 4) manufacturer support for filing of compassionate use exemptions for device maintenance, etc.

 

Delayed Onset Study

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

Since applications proposing delayed onset trials are not responsive to this RFA (see Section I), this attachment must not be used.

PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

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.

In addition to the items described in the policy, letters and documentation of communications with regulatory bodies, including the FDA or IRB, may be submitted as post-submission materials (NIH post-submission deadline applies).

 

Communications with the IRB.

  • For projects requiring non-clinical testing to support an IRB NSR designation, preliminary communications (e.g., letter or other documentation) with the IRB indicating what non-clinical testing will be necessary to support the NSR clinical trial should be included with a description of how the feedback will be incorporated . This document must not exceed 5 pages.

 

Communications with FDA

  • Applicants should include minutes from all pre-submission meetings, notice of IDE, risk determination, email communications, and other relevant documentation. This material should only be submitted in section 4.6.a of the application or as post-submission material.
  • Large animal safety studies are often required by the FDA to support an IDE. Applicants should include a large animal GLP safety study conducted on the full-final device system using the final manufacturing process intended to support the IDE. If a large animal safety study is not required by the FDA for an IDE, or a test of the full final system using final design and manufacturing processes is not required, applicants should include a communication from the FDA clearly stating this is the case in the form of a response to a Pre-Submission. If these studies are proposed, but ultimately not needed, program staff will work with the investigators to remove the relevant milestones and associated costs of these activities from the award. This document must not exceed 30 pages.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

 

For this particular announcement, note the following:

The market size for the proposed types of therapeutic or diagnostic devices through this request for applications 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.

 

The UG3/UH3 Cooperative Agreement grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or from investigator-generated data.  Accordingly, the evaluation will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.

 

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.

 

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

For this particular announcement, note the following:

Supporting Data for Entry:

  • If included, does the FDA Pre-Submission (formerly pre-IDE) feedback indicate that the proposed pre-clinical testing plan is sufficient to support a successful FDA submission for an IDE by the end of the UG3 phase? Or for Non-Significant Risk (NSR) studies, do the preliminary communications with the IRB indicate that the proposed pre-clinical testing plan is sufficient to support the NSR clinical trial?

Needs Assessment :

  • Is the needs assessment adequate and complete?
  • Does the needs assessment incorporate input from all relevant stakeholders (patients, clinicians, caregivers)?

 

In addition, for applications involving clinical trials

 

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy?  For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

 

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?

For this particular announcement, note the following:

Team Management Plan (PHS Human Subjects and Clinical Trials Information, Section 3.5):

  • Has an interdisciplinary team been assembled, and have experts in pre-clinical development and clinical development been appropriately included in the conception, design, and proposed implementation of the project?
  • Evaluate the adequacy of the level of expertise and experience of the investigative team for preclinical, regulatory, and clinical components of the project. Are there any concerns about the investigative group's ability to move the device forward into a trial in humans?
  • Has a Scientific Steering Group (SSG) been described and are the members appropriate?

 

In addition, for applications involving clinical trials

 

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

 

 

 

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?

For this particular announcement, note the following:

  • How significant of an advantage does the proposed device offer over all existing approaches as well as those in development for the same indication regardless of therapeutic classes, including drugs, biologics, as well as competing device technologies?
  • If the proposed device is designed to improve over early generations that may or may not have been marketed, are the potential advantages truly significant? Are those changes likely to succeed where the predecessor did not?

 

In addition, for applications involving clinical trials

 

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

 

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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?

In addition, for applications involving clinical trials

 

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

 

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

 

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

 

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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 children, justified in terms of the scientific goals and research strategy proposed?

 

For this particular announcement, note the following:

Overall device development plan:

  • Is the overall plan for device development reasonable, including the plan after conclusion of the proposed trial?

  • Are there clear metric driven design criteria developed with input from stakeholders? Is the regulatory plan reasonable in terms of regulatory path to market as well as FDA data requirements to meet the appropriate regulatory standard (e.g., reasonable assurance of safety and effectiveness for PMA submissions, substantial equivalence for 510(k) submissions)?

Detailed Plans for Research Strategy:

  • Will the implementation of the overarching plan lead to the development and testing of the proposed therapeutic or diagnostic device?

  • Is a large animal safety study performed utilizing GLP proposed or is there a clear reason that a large animal study will not be necessary to support an IDE (e.g., communication from the FDA)?

  • Will the project reach an IDE or IRB approval for a non-significant risk (NSR) study at end of the UG3 phase?

If Applicable - Long Term Plan for Patients (PHS Human Subjects and Clinical Trials Information, Section 5.1):

  • Is the plan for care of patients at the end of the study reasonable?

  • If appropriate, is care for patients beyond the study period described?

 

 

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?

For this particular announcement, note the following:

  • Is there sufficient regulatory and intellectual property resources present to facilitate project milestones and deliverables?
  • Is the environment at the applicant institution or the subcontracting organization sufficient to support any proposed GMP and GLP activities?

 

In addition, for applications involving clinical trials

 

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

 

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

 

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

 

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

 

 

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.

 

Study Timeline

Specific to applications involving clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment?

Is the projected timeline feasible and well justified?

Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? 

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

 

Milestone Plan

  • Are milestones timely and robust and associated with clear, quantitative criteria for efficacy and success that allow go/no-go decisions?
  • Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
  • Are there additional key experiments that need to have milestones?
  • Does the provided Gantt chart demonstrate a reasonable timeline for the project plan?

 

 

For research that involves human subjects but does not involve one of the six 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 six 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.

 

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 children 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.

 

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.

 

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.

 

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.

 

Not Applicable

 

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 (IP) strategy:

    • Are potential issues regarding the IP landscape for the device being developed and means for addressing any IP hurdles/barriers addressed? Do the IP Strategy attachment and related letters of support address potential concerns?
    • Are there any known constraints that could impede the development of the device?
    • Are IP filing plans described and appropriate?

 

Not Applicable

 

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).

 

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).

 

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.

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 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 Institute of Neurological Disorders and Stroke Advisory Council. 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. 

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/ 

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.  Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE). 

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.

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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.

Cooperative Agreement Terms and Conditions of Award

T he 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 Parts 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 objectives and approaches, and for planning, conducting, analyzing, interpreting, drawing conclusions on their studies, publishing and sharing the results.
  • Developing and proposing rigorous milestones that will be achieved during the project period.
  • Retaining custody of and have all rights to the data and technology developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
  • Pursuing patent protection , as appropriate and consistent with the terms and conditions of the award and goals of the program .
  • Providing progress reports with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not. In cases when NIH program staff request raw data, awardees agree to provide the data.
  • Participating at least twice a year in progress meetings (teleconferences) that are organized by NIH staff.
  • Communicating regulatory meeting dates and agenda to the NIH program staff and invite their participation.
  • Communicating study reports from CROs, meeting minutes (and associated data packages if applicable), letters and other forms of communications with FDA, Recombinant DNA Advisory Committee (RAC), and other authorities, and to provide IND# and registration numbers in clinical trial.gov, if applicable.
  • Providing regulatory and clinical documents that are required for administrative review.
  • Verifying that the clinical trial is performed in accordance with Good Clinical Practices (GCP) and all IC specific guidelines for data and safety monitoring in clinical trials (e.g. NINDS Guidelines for Data and Safety Monitoring in Clinical Trials:  http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm, and must provide data and regular updates to NIH.

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

  • Each project will have the support of one or more Project Scientists from NIH program staff who are assigned an administrative role for the nervous system disorder(s) being studied and have expertise in the implementation of translational research.
  • The NIH Project Scientists will have substantial scientific/programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.
  • NIH Project Scientist(s) provides input on the milestones and makes decisions regarding their finalization.
  • NIH Project Scientist(s) will be responsible for assessing the progress of the project towards the specified milestones, and for recommending if further funds should be released to the project.
  • NIH 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.
  • NIH Project Scientist(s) participates in meetings together with PIs with regulatory agencies related to the funded project.
  • An important part of the program is the coordination of research efforts across different funding mechanisms and research capabilities, and the coordination among efforts aimed at different nervous system disorders. NIH Project Scientists will have the primary responsibility for this overall coordination.
  • Additionally, an NIH Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
  • 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 robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NIH portfolio balance and program priorities, competitive landscape, and availability of funds.

 

Areas of Joint Responsibility include:

Clarifying and negotiating the milestones and timelines.

 

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 for the investigators 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 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. Final decisions made by NIH regarding a discontinuation are not appealable.

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 on-time submission, 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 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)

Nick Langhals, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email:nick.langhals@nih.gov

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

Wen G. Chen, MMSc, PhD
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-451-3989
Email: chenw@mail.nih.gov

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

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

Soundar Regunathan, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Phone: 301-443-1192
Email: regunathans@mail.nih.gov

Charles H. Washabaugh, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5050
Email: Charles.Washabaugh@nih.gov

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

Kevin Walton
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5980
Email: kevin.walton@nih.gov

Yolanda F. Vallejo, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301.827.4655
E-mail: yolanda.vallejo@nih.gov

Teresa L.Z. Jones, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-2996
Email: teresa.jones@nih.gov

David McMullen, M.D.
National Institute of Mental Health (NIMH)
Telephone: 301-451-0180
Email: david.mcmullen@nih.gov

Augie Diana, Ph.D.
National Institute of Nursing Research (NINR)
Telephone: (301) 402-6423
Email: dianaa@mail.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Tijuanna E. DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.nih.gov

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

Shelley Carow
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301.594.3788
Email: carows@mail.nih.gov

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

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

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: jfox@mail.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)
Tel: (301) 594-7760
Email: edgertont@mail.nih.gov

Bryan S. Clark, MBA
Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-0915
Email: clarkb1@mail.nih.gov

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: pfleming@nida.nih.gov

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

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

Rebecca Claycamp
National Institute of Mental Health (NIMH)
Telephone: 301-443-2811
?E-mail: rclaycam@mail.nih.gov

Kelli Oster
National Institute of Nursing Research (NINR)
Telephone: 301-594-2177
Email: osterk@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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