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 Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

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 on Drug Abuse (NIDA)

National Institute of Mental Health (NIMH)

National Center for Complementary and Integrative Health (NCCIH)

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 Behavioral and Social Sciences Research (OBSSR)

Funding Opportunity Title
Blueprint MedTech Translator (UG3/UH3 - Clinical Trial Optional)
Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-21-315
Companion Funding Opportunity
PAR-21-282 , U44 Blueprint Medtech: Small Business Translator (U44 - Clinical Trial Optional)
PAR-21-314 , U54 Blueprint MedTech: Incubator Hubs (U54 Clinical Trial Not Allowed)
Assistance Listing Number(s)
93.853, 93.865, 93.866, 93.867, 93.286, 93.279, 93.273, 93.121, 93.213, 93.242
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage investigators to pursue translational activities and clinical feasibility studies to advance the development of therapeutic, and diagnostic devices for disorders that affect the nervous or neuromuscular systems.

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 clinical feasibility study. The clinical study 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 FOA is a milestone-driven cooperative agreement program and will involve participation of NIH program staff in negotiating the final project plan before award and monitoring of research progress.

Participants in Blueprint MedTech receive funding for all activities to be conducted in their own laboratories. In addition, applicants will collaborate with NIH-funded consultants to receive assistance with specialty areas including regulatory, reimbursement, intellectual property, commercialization, and strategic partnerships. Participants can also augment their project with NIH contract research organizations that specialize in large animal testing, sterilization testing, biocompatibility assessment, manufacturing, and medical monitoring.

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 any of the companion opportunities. For more information see BP MedTech website: https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-medtech

Key Dates

Posted Date
August 20, 2021
Open Date (Earliest Submission Date)
September 20, 2021
Letter of Intent Due Date(s)

60 days prior to the application due date.

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 20, 2021 October 20, 2021 Not Applicable March 2022 May 2022 July 2022
February 18, 2022 February 18, 2022 Not Applicable July 2022 October 2022 December 2022
June 20, 2022 June 20, 2022 Not Applicable November 2022 January 2023 April 2023
October 18, 2022 October 18, 2022 Not Applicable March 2023 May 2023 July 2023
February 21, 2023 February 21, 2023 Not Applicable July 2023 October 2023 December 2023
June 19, 2023 June 19, 2023 Not Applicable November 2023 January 2024 April 2024
October 18, 2023 October 18, 2023 Not Applicable March 2024 May 2024 July 2024
February 20, 2024 February 20, 2024 Not Applicable July 2024 October 2024 December 2024
June 20, 2024 June 20, 2024 Not Applicable November 2024 January 2025 April 2025

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
June 21, 2024
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

Blueprint MedTech

The NIH Blueprint for Neuroscience Research is a collaborative framework through which 14 NIH Institutes, Centers and Offices jointly support neuroscience-related research, with the aim of accelerating discoveries and reducing the burden of nervous system disorders (for further information, see http://neuroscienceblueprint.nih.gov/).

Innovators developing groundbreaking medical device technologies face a number of challenges along the translational path from bench to bedside. The Blueprint MedTech program is an NIH incubator that aims to address such challenges and support the innovators by accelerating the development of cutting-edge medical devices to diagnose and treat disorders of the nervous system. The mission of the program is to catalyze the translation of novel neurotechnologies from early-stage development to first-in-human clinical studies. The program will provide: (a) non-dilutive funds to support medical device development activities led by investigators, and (b) additional resources and support services including, but not limited to:

  • Planning resources to support concept development, team building, needs assessment, and other early translational activities.
  • Streamlined access to translational services and expertise (e.g., design and prototyping, bench testing, large animal testing, biocompatibility assessment, manufacturing, medical monitoring).
  • Assistance from consultants (e.g., on regulatory, reimbursement, intellectual property, commercialization, and strategic partnership issues).
  • Advice from industry experts (e.g., meetings with an external oversight committee).

The overarching goal of the Blueprint MedTech program is to accelerate patient access to groundbreaking, safe, and effective medical devices. The program will provide support to sufficiently develop and de-risk technologies to the point where additional investments are warranted from industry partners, investors, and government.

A. Overview

The purpose of this Funding Opportunity Announcement (FOA) is to support grantees in pursuing translational activities and clinical studies to advance the development of therapeutic, and diagnostic devices for disorders that affect the nervous or neuromuscular systems. Activities supported by this FOA include implementation of clinical prototype devices, non-clinical safety and effectiveness testing, design verification and validation activities. Additional activities include 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 support for a subsequent clinical feasibility study. The clinical study 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.

All projects must have two phases: UG3 and UH3. The UG3 phase will support non-clinical testing to obtain an IDE and IRB approval for an SR clinical study, or to obtain IRB approval for an NSR clinical study. All projects will start at the UG3 phase. The duration of the UG3 phase will depend on the maturity of the project at entry and can range from one to four years. Only those UG3 phase projects that have met specific criteria (see below) will transition to the UH3 phase after NIH administrative review. The UH3 phase will support a clinical feasibility study and can last one to four years, however, the total project period (including both the UG3 and UH3 phases) must not exceed five years. Furthermore, ethical considerations are intrinsic to the responsible conduct of neuroscience research and the translation of neuroscience advances (scientific and technological) into clinical practice. Projects for which only a clinical phase is proposed are outside of the scope of this funding opportunity.

This FOA utilizes a UG3/UH3 cooperative agreement mechanism. As a cooperative agreement, this FOA supports milestone-driven projects and involves NIH program staff’s participation in negotiating project and milestones plan before award, monitoring the research progress, and making go/no-go decisions. The expectations of the program are in line with those of industry regarding the advancement of devices through the developmental and translational pipelines. As such, an inherent rate of attrition is possible within this program.

An objective of this program is to foster and encourage participation in innovation and entrepreneurship by socially and economically disadvantaged persons and women-owned small businesses. This PAR encourages applications from diverse teams of investigators,including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce(see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27 and the most recent report on Women, Minorities, and Persons with Disabilities in Science and Engineering). Such individuals include those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds.

B. Scope

Projects must focus on a disorder that falls within the mission of participating NIH Blueprint Institutes and Centers. It is expected that devices within the scope of this program either:

C. Entry criteria

Applicants to the Blueprint MedTech program must include novel medical device technologies that will advance upon current neurotechnology (see non-responsive criteria below).

Applicants should clearly define the current state of the art and highlight how their proposed technology will advance patient care. Responsive applications should propose medical devices, expected to be regulated by the FDA, with first-of-its-kind technologies, unique and novel intended use, new safety questions, and/or new regulatory questions. Responsive applications may also pivot and refine existing technologies toward new intended use and/or use in novel settings (e.g., innovating and translating a neuromodulation device approved for healthcare-setting only to home-use).

Proposed medical devices and their indications will likely follow De Novo or Premarket Approval (PMA) regulatory pathways. Medical devices with indications that may fit within an existing 510(k) pathway may also be accepted, as long as the application can demonstrate a clear clinical and technological innovation beyond the state of the art of existing FDA-cleared predicates. Such devices should be reasonably expected to provide new clinically meaningful diagnostic or therapeutic options or improve the benefit-risk profile of a treatment or diagnostic through substantial safety innovations.

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 key stakeholders (e.g., clinicians, patients, and caregivers) as well as supporting literature.
  • A compelling case for a successful IDE submission for an SR study or IRB approval for an NSR study. Required regulatory approvals for clinical studies must be in place prior to the start of 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 of the UG3 phase of the award. Funding may 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. Any remaining funds associated with the original award will not be released.

D. Phases

UG3 phase:
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 or diagnostic parameters, and refine device design as necessary for subsequent GLP testing or additional clinical studies 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.
  • Studies addressing usability or acceptability
  • Device, software, firmware, and cybersecurity, 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 Device Exemption (HDE), Request for Risk Designation, 513(g) submission).

UH3 phase:

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

  • A marketing application if the clinical study is sufficiently powered to demonstrate device safety and effectiveness for regulatory approval; or
  • A larger clinical study 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 studies and eventual market approval
  • Studies of the key physiological variables that may impact the function of the device in humans; and
  • Initial assessments of device safety are expected, but only in conjunction with obtaining enabling data about device design or function

E. Non-Responsive Activities

Applications that include the following activities will be considered non-responsive and will be withdrawn and not reviewed:

  • Animal model development: all in vivo models must be established and characterized, and available to the applicant;
  • Efforts to develop neurotechnology for fundamental study of the nervous system;
  • Fundamental basic/applied research projects that employ existing market approved devices for their labeled uses;
  • Projects focused on technologies for augmentation of healthy individuals;
  • Delayed-onset clinical studies;
  • Device technologies not regulated by the FDA.

Applications that do not include the following other attachments will be considered incomplete:

 

  • Needs Assessment
  • IP Strategy
  • Gantt Chart
  • Long-term care plan
  • Resource Checklist
  • A milestone plan;

It is recommended that applicants reach out to the NIH program staff listed at the bottom of this funding opportunity to discuss responsiveness criteria with respect to proposed technologies and indications.

F. Milestones

Because device development is inherently risky, it is anticipated that there may be attrition as projects progress. Applications must propose one or more milestones for each objective in each year of the project. Milestones are goals that quantitatively measure success and efficacy that will be used for go/no-go decision-making for the project (see below for details).

For each milestone, provide details on methods, assumptions, experimental designs, and data and statistical analysis plans (if the results are quantitatively measured). Specify the quantitative criteria for measuring success and the rationale used to develop and justify the quantitative criteria identified. Quantitative criteria should be robust and consistent with the state-of-the-art in the field. Applicants are encouraged to read examples of milestones (e.g., https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library/Devices-Milestones).

NIH program staff will contact the applicant to discuss the project and any changes prior to funding the application, including negotiation of the proposed milestones. 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 yearly by NIH program staff. Program staff may involve independent consultants or subject matter experts with relevant expertise. If justified, future milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the 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.

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 be transitioned into the UH3 phase based on the following:

  • Successful achievement of the defined milestones for the UG3 phase of the project;
  • Likelihood of success in clinical testing;
  • Competitive landscape;
  • Programmatic priorities and current portfolio balance (for funded projects, search NIH RePORTER https://projectreporter.nih.gov/);
  • For significant risk studies, documentation of final or conditional approval of the IDE 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 human subjects obtained from the Safety and Risk Assessment Committee (SARAC) of the relevant Institute;
  • Agreement on updated timeline, milestones, and budget for the clinical study; and
  • Availability of funds.

G. Quality and Compliance Requirement

The use of the Design Control and Quality Systems processes (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/design-control-guidance-medical-device-manufacturers) 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.

H. 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.

I. Pre-application Consultation

As an UG3/UH3 cooperative agreement, NIH program staff will be involved in the negotiation and execution of the projects. Applicants are strongly encouraged to consult with NIH program staff when planning an application. Early contact provides an opportunity for staff to provide further guidance on program scope, goals, and developing appropriate milestones. When possible, applicants should contact program staff at least 12 weeks before a receipt date.

J. Institute Statements of Interest

Refer to Blueprint MedTech website for specific IC requirements and interest statements: https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-medtech/blueprint-medtech-ics-and-contacts

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. Only those application types listed here are allowed for this FOA.

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

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. 

Award Budget

Application budgets are not limited but need to reflect the actual needs of the proposed project. In all cases, applicants should propose a budget that is reasonable and appropriate for completion of the research project. Application budgets should only cover the work that will be performed by the PD/PI and his/her staff. The NIH will pay Blueprint MedTech contractors and consultants directly for their work; therefore, these expenses should not be included in the budget for this application.

Award Project Period

The proposed project period for the UG3 phase must not exceed 4 years.

The proposed project period for the UH3 phase must not exceed 4 years.

The total duration of the UG3 and UH3 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)

Local 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)

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the 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.

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

Telephone: 301-496-1779

Email: Blueprint-MedTech@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.

Other Attachments:

Gantt Chart (Required – 1-page max):

Applications that exceed this limit or do not include this attachment will be withdrawn. This attachment should be entitled "Gantt.pdf". Applicants should include a project timeline in the form of a Gantt chart (or similar) that includes all major tasks to be performed during the project. The chart should also include estimated start and completion dates for those tasks.

Intellectual Property (IP) Strategy (Required – 3 pages max):

Applications that exceed this limit or do not include this attachment will be withdrawn. This attachment should be entitled "IP Strategy.pdf". Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

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 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. IP landscape considerations and constraints to be addressed include:

  • If the applicant proposes using a device or technology whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, 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 if there is agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.
  • If patents pertinent to the therapeutic 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 (see below).

Needs Assessment (Required – 3 pages max):

Applications that exceed this limit or do not include this attachment will be withdrawn. This attachment should be entitled "Needs Assessment.pdf". The Needs Assessment should:

  • Establish performance requirements with clear, quantifiable metrics.
  • 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.
  • 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; and
  • Identify any human factors (i.e. ergonomics) incorporated into the proposed research that optimize human interaction, productivity, and understanding while using the technology.

Long-term Care Plan for Patients (Required – 3 pages max):

Applications that exceed this limit or do not include this attachment will be withdrawn. This attachment should be entitled "Long-term Care.pdf" which will be reflected in the final image. First, applicants should describe the anticipated care needs of participants after a trial has ended, which are related to their trial participation (e.g., continued access to the device, device maintenance, and/or device explant). Where relevant, it is recommended that applicants consider various posttrial scenarios, such as device and trial failure or success, regulatory approval options, and decisions by device manufacturers to commercialize or discontinue a product.

Second, applicants must describe a plan for the care of patients at the end of the study and after the study period, if appropriate, related to the potential care needs. These plans may vary from project to project, depending on, for example, whether patients are likely to have other ways to access this care, the anticipated risks and benefits of receiving this care, the anticipated risks and benefits of not receieving this care, and the feasibility of facilitating this care. Plans might include, for example:

  • explant of indwelling devices once the approved study period is complete,
  • surgical removal of batteries and ‘capping’ the exposed metals from leads/IS-1 connectors,
  • manufacturer-supported device maintenance for patients responding to therapy,
  • manufacturer support for filing of compassionate use exemptions for device maintenance, etc.

All plans should include information regarding post-trial obligations (e.g., explantation, hardware and software maintenance and/or updates, or device-related medical expenses).

Resource Checklist (Required - 2 pages max):

Applications that exceed this limit or do not include this attachment will be withdrawn. This attachment should be entitled "Resource Checklist.pdf". The Blueprint MedTech program intends to support grantees by providing commercialization, verification, and validation resources. Applicants are required to identify which of the following resources provided by Blueprint MedTech program will be utilized from the list below:

  • Prototype Development
  • Electronics Manufacturing
  • Electrical safety
  • Electromagnetic compatibility testing
  • Magnetic resonance testing
  • Computational Modeling
  • Software Testing Documentation
  • Cybersecurity Testing and Documentation
  • Biocompatibility, chemical characterization, extractable/leachable, and biocompatibility risk assessment
  • GLP-compliant animal testing
  • Sterilization, packaging, and shelf life testing
  • Clinical trial support including central IRB, DSMB, and trial design
  • Regulatory strategy consulting
  • IP protection
  • Good Manufacturing Practice, Quality Management System, and Compliance Management
  • Business Development, Market/User Research, and Commercialization

Applicants are furthermore encouraged to indicate that these resources will be provided by BP MedTech by inserting a statement along the lines of “If selected for funding, we expect that the following resources will be made available to this project by the Blueprint MedTech program. Since the program will provide these resources at no cost, this application does not request any labor or budget associated with these resources.” Applicants should provide justification for why any of the above activities are not being utilized in the current application.

Schematics (Optional – 1 page max):

Applications that exceed this limit will be withdrawn. This attachment should be entitled “Schematics.pdf”. This attachment may include images, photos, drawings, engineering schematics, design specifics, and associated labeling and captions.

Communications with the IRB (Optional – 5 pages max):

Applications that exceed this limit will be withdrawn. This attachment should be entitled “IRB Communications.pdf”. Applicants should submit relevant approval letters and associated attachments.

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 study.

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

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 study.

Research Strategy

The single Research Strategy attachment must include the following subsections:

Significance

A. Clinical Impact and Feasibility

Please note that each application should focus on only one neurological disorder or disease, even if the device proposed for development could be used for more than one indication. The target patient population and intended use should guide the design of the device and of the proposed clinical activities.

  • 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 or diagnostic class (i.e., agents and devices).
  • Describe the significant advantages of the proposed device over early generations that may or may not have been marketed and why this iteration is likely to succeed where the prior iterations were insufficient (if applicable).
  • 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 current therapy development or significant efforts underway in academia and industry, including both neurotherapeutics and devices.
  • Describe both the minimally acceptable and ideal results of the proposed clinical study and explain the rationale for each.

B. Supporting Data for Entry

The Supporting Data for Entry section should contain, at a minimum, comprehensive data and information that validate the feasibility of conducting studies to address the specific aims. When presenting preliminary results, details about study design, execution, analysis, and interpretation must be included. PD(s)/PI(s) should explain the choice of models or assays used to collect preliminary data, and primary, secondary and exploratory endpoints collected and how they are clinically relevant.

  • For novel devices, proof-of-concept data of device function are required. These data must be obtained using a prototype device that is close to the final device design anticipated for clinical testing, ideally tested in an animal model representative of the intended patient population. Sufficient detail of the device design should be included such that a comparison between the device used to collect preliminary data and the proposed device can be made.
  • For any device, the supporting data for entry should include a description of the device and its capabilities with sufficient detail for reviewers to assess if the device is appropriate for use in the proposed clinical activities.
  • A clear schematic, drawing, and/or image should be included along with the device description as an optional attachment (see above, Other Attachments- Schematics).
  • Applicants should justify the type of stimulation proposed (if applicable), target(s), and patient population.
  • For applications proposing first-in-human studies, preliminary data in humans are not required.
  • The application should present a credible path towards an IDE or an NSR clinical study. As such, pre-submission feedback from the FDA or preliminary communications with the IRB, if included, should indicate that the proposed pre-clinical testing plan is sufficient to support a successful FDA submission for an IDE by the end of the first phase or IRB approval for an NSR clinical study.

Approach

A. Technology Translation Plan:

Applicants must include an overall plan for device development and translation to outline how the proposed technology will be adopted into clinical practice, based on the work included in the application and beyond.

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.
  • Evidence of contact with appropriate U.S. regulatory bodies (e.g., FDA in the form of pre-submission meetings and IDE submission), if available, should indicate that the regulatory path to market is reasonable.
  • A description of what methods/procedures/approaches used in current clinical practice will change as a result of the adoption of this technology,
  • An estimated timeline for when clinical adoption will be feasible, highlighting key benchmarks (e.g., pivotal study, regulatory approval, widespread implementation, clinical adoption),
  • A discussion of any additional studies needed and why,
  • Key stakeholders and how they will be engaged for each step, and
  • A description of any anticipated obstacles that could delay or subvert adoption and potential ways to address/mitigate those obstacles.

B. 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 study (UH3 phase) should be included in the PHS Human Subjects and Clinical Trials Information form. Blinding, randomization, power analysis for sample size, and independent replication should be included in the application wherever possible.

UG3 phase: Non-clinical activities in the UG3 phase should include:

  • A project plan compatible with an accelerated timeline to obtain approval to conduct the clinical study.
  • A clearly stated device testing timeline that includes quantifiable, practical, achievable goals in support of the proposed clinical study.
  • A description of all non-clinical testing necessary to support the filing of an IDE or to obtain IRB approval for an NSR clinical study, 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 FDA (e.g., pre-submission meetings and/or IDE submission), if applicable.
  • Plans for all necessary benchtop and animal studies required by the FDA to support an IDE, if applicable. Biocompatibility and large animal safety studies (e.g., canine, porcine, ovine, etc.) are often required by the FDA and should be considered in this section (https://www.fda.gov/medical-devices/investigational-device-exemption-ide/ide-related-topics).
  • 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 applicable.
  • 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 4.5.a).
  • 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 study.
  • 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.

C. Milestones and Timeline:

Applications must include a milestone plan.Milestones should be associated with clear, quantitative criteria for measuring success and efficacy that can be used for go/no-go decision making

UG3 Phase:

  • Go/no-go criteria should be specified for transitioning from the UG3 Phase to the UH3 Phase.
  • Milestones should be included that focus on 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 study, 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.

UH3 phase:

  • Information related to human subjects and clinical studies that supports the UH3 research strategy (including milestones and timeline) should be included in the PHS Human Subjects and Clinical Trials Information form. Investigators should clearly articulate what the next step will be in technology translation assuming a successful outcome of the clinical study and justify the outcome metrics for the proposed clinical study in terms of quantifiable minimum-success criteria necessary to enable this next step.

Letters of support:

Applicants should include letters 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 intellectual property associated with this project.
  • If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
  • If collaborating with a private entity, include a letter of support from that private entity that states whether they are agreeing to provide the device or technology, if there is any limit on the studies that can be performed with that device or technology, limitations on sharing of data, and whether licensing agreements are in place.
    • If collaborating with a contract research or manufacturing organization (CRO / CMO), a letter of support can summarize results of tests that have been performed, but should not contain detailed results of all testing (2 pages max).

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:

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 human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.7 Study Timeline

Attachment: 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 / non-responsive and will not be peer reviewed.

  • Applicants should include a timeline and quantitative milestones for completion of key stages of the study, 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.
  • Applicants are strongly encouraged to hold a pre-submission meeting with the FDA to discuss the clinical study protocol prior to submission of an IDE, as described above. If the stated goal of the clinical feasibility study is to obtain data to support a marketing application, then a clear non-binding indication that the proposed clinical study protocol is likely sufficient for that purpose must be obtained during this pre-submission meeting.
  • A patient engagement timeline should be included as either text or graphical depiction. This timeline should include major activities performed by or with patients as part of the study (e.g., patient enrollment, implants, assessments, data collection).

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 individuals across the lifespan (as appropriate);
  • Completion of interim analyses and safety assessments;
  • 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; and
  • Other protocol-specific performance milestones and timeline.

Section 3 - Protection and Monitoring Plan

3.1 Protection of Human Subjects

In addition to the standard components, this section should include a Neuroethics section. Ethical considerations are intrinsic to the responsible conduct of neuroscience research and the translation of neuroscience advances (scientific and technological) into clinical practice. Applicants are required to describe the ethical considerations related to:

  • The design and conduct of the proposed study (e.g., for trials in which research is ancillary to a clinical procedure or without a prospect of benefit to participants). Therapeutic misconception may be a concern and/or the appropriateness of the risks of the study may require consideration.
  • The potential (long-term) implications of the proposed study (e.g., the potential psychosocial or legal implications for patients of developing predictive biomarkers for pre-symptomatic individuals).

Where relevant, applicants should describe how these ethical considerations are addressed in the study design and monitoring plan addressing the guiding principles below (see Neuroethics Guiding Principles for the NIH BRAIN Initiative for additional considerations).

  • Make assessing safety paramount
  • Anticipate special issues related to capacity, autonomy, and agency
  • Protect the privacy and confidentiality of neural data
  • Attend to possible malign uses of neuroscience tools and neurotechnologies
  • Move neuroscience tools and neurotechnologies into medical or nonmedical uses with caution
  • Identify and address specific concerns of the public about the brain
  • Encourage public education and dialogue
  • Behave justly and share the benefits of neuroscience research and resulting technologies

3.3 Data Safety and Monitoring Plan

Attachment: DSMP: Applicants must submit a data safety and monitoring plan and should consider Guidelines and Policies for Monitoring Clinical Research in the formation of the plan as required by the appropriate IC. Applicants should.

  • In addition to the general guidelines include an adequate description and justification of safety risks to participants that includes risks incurred during the trial and for device removal. This description should incorporate how risks will be mitigated.
  • Describe the handling of participant recruitment and informed consent or assent, including who will obtain informed consent, methods used to avoid therapeutic misconception, and any added considerations for obtaining and/or maintaining informed consent or assent from vulnerable participant populations (if applicable).
  • Include adequate scientific justification for inclusion/exclusion criteria. Exclusion criteria should avoid discrimination against particular groups.
  • Describe plans to incorporate an independent committee to evaluate data safety and monitor patient safety
  • Describe any plan to address cybersecurity and confidentiality of participants’ personal data (if applicable).

3.5 Overall Structure of Study Team

Attachment: Team Management Plan (Required – 2 pages max): Applications that exceed this limit or do not include this attachment will be withdrawn. NIH strongly encourages applicants to form diverse multidisciplinary teams that consist of non-clinical and clinical scientists, disease experts, regulatory experts, bioethics specialists, experts in manufacturing under Quality Systems and Design Controls, and other relevant academic, clinical, and/or industry experts including individuals who are underrepresented in the biomedical workforce (defined in NIH NOT-OD-20-031). This team should have the expertise to clearly define gaps to be addressed during this funding period, to develop the details of the project plans and experiments, and to successfully execute the research strategy and clinical study. 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

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

Attachment: FDA Communications:

  • Applicants should include a summary (1-page max) of interactions with the FDA supported by the following documentation (10 pages max), which should be attached: approved minutes from all pre-submission meetings, notice of IDE approval and any associated attachments (if applicable), risk determination, breakthrough device designation (if applicable), 513(g) letter (if applicable), communications on official FDA letterhead, and email communications with substantive information regarding the device, review, or outcome. This material should only be submitted in section 4.5.a of the application or as post-submission material. Pre-submissions themselves should not be included in the application or as an attachment.
  • 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.
Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed onset trials are not responsive and will not be accepted.

PHS Assignment Request Form

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide

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.

IRB Communications (Optional – 5 pages max):

  • Submissions that exceed this limit will not be accepted.
  • This attachment should be entitled “IRB Communications.pdf”.
  • Applicants should submit relevant approval letters and associated attachments.
  • 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 study

FDA Communications (Optional - 10 pages max):

Applicants should include a summary (1-page max) of interactions with the FDA, supported by the following associated and attached documentation):

  • approved minutes from all pre-submission meetings
  • notice of IDE approval and any associated attachments
  • notification of risk determination
  • breakthrough device designation
  • 513(g) letter (if applicable)
  • communications on official FDA letterhead
  • email communications with substantive information regarding the device, review, or outcome.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

  • 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.

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.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Specific to this announcement:

Supporting Data for Entry:

  • For a novel device, was the proof-of-concept data on device function obtained using a prototype device that is close to the final device design?
  • Are the device and device capabilities appropriate for use in the proposed clinical study?
  • Is justification provided for the type of stimulation proposed, neural target(s), and patient population?
  • 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 that the proposed pre-clinical testing plan is sufficient to support the NSR clinical study?

Needs Assessment (attachment):

  • Is the needs assessment adequate and complete?
  • Are performance requirements established with clear, quantifiable metrics?
  • Does the needs assessment incorporate input from all relevant stakeholders (patients, clinicians, caregivers) regarding the device performance requirement(s) for the clinical issue to be addressed?
  • Were the needs of the beneficiaries of the proposed research appropriately identified?

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?

Investigator(s)

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

Specific to this announcement:

Team Management Plan (attachment):

  • Does the project engage a diverse multidisciplinary team(s) consisting of clinicians, scientists, device engineers, data/computational scientists, regulatory specialists, and/or ethics specialists, as appropriate?
  • Evaluate the adequacy of the level of expertise and experience of the investigative team for non-clinical, clinical, regulatory, manufacturing, and other relevant components of the project.
  • Is the team’s governance and organizational structure appropriate for the support of the research project?
  • 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?

Innovation

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

Specific to this announcement:

  • How significant of an advantage does the proposed device offer over all existing clinically available approaches for the same indication regardless of therapeutic or diagnostic classes, including drugs, biologics, as well as competing device technologies?
  • If the proposed device is designed to improve over early generations, are potential advantages justified? Are the changes in the proposed device likely to succeed where the predecessor did not?
  • Does the proposed device reduce the occurrence of (i) a known serious adverse event, (ii) a known device failure mode or (iii) use related hazard or error, or offer an improvement in the safety or of another device or intervention?

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?

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this announcement:

Technology Translation Plan

  • Is the overall plan and timeline for device development reasonable, including the plan after conclusion of the proposed study?
  • 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)?
  • Does the application describe what methods/procedures/approaches will change due to the adoption of the proposed technology?
  • Does the estimated timeline for clinical adoption indicate feasible key translation benchmarks for adoption into clinical practice?
  • Does the plan address whether and how key stakeholders will be engaged at each step?
  • Are any additional needed studies described and justified? Are anticipated obstacles described along with potential strategies for address these obstacles?

Detailed Plans for Research Strategy:

  • Will the implementation of the overarching plan lead to the development and testing of the proposed therapeutic device?
  • If applicable, is any non-clinical testing planned that will be needed to support the filing of an IDE or to obtain IRB approval for an NSR clinical study?
  • Is a large animal safety study proposed that will be performed utilizing GLP and the final device design 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)?

Long-term Patient Care Plan (Attachment):

  • Has the applicant anticipated the key long-term care needs that patients may have, related to trial participation?
  • Is the plan for care of patients at the end of the study reasonable, and does it consider various post-trial scenarios?
  • Does the long-term patient care plan address whether patients are likely to have other ways to access post-trial care, the anticipated risks and benefits of receiving this care, the anticipated risks and benefits of not receiving this care, and the feasibility of facilitating this care can be considered in this determination?
  • If applicable, does the plan address financial liability for injury, device removal, device revision, and management of in-dwelling devices either during or after the study?

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?

Environment

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

Specific to this announcement:

  • Are there sufficient regulatory resources on the team to facilitate regulatory consultations and approvals?
  • Is the environment at the applicant institution or the subcontracting organization sufficient to support any proposed GMP and GLP activities?
  • Have the applicants adequately justified the selection of resources they will need to be provided by the BP MedTech program? Have applicants justified why they do not need to utilize the available BP MedTech resources that are not selected?

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 and Milestone Plan

    UG3 Phase:

    • Does the Gantt chart provide sufficient detail of the projected timeline with key project tasks? Do these details demonstrate feasible and well-justified plan for completion of the study?
    • Are milestones timely and robust and associated with clear, quantitative criteria for efficacy and success that allow go/no-go decisions?
    • Are go/no-go criteria specified for transitioning from the UG3 Phase to the UH3 Phase?
    • Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
    • Are milestones included that reflect the planned regulatory requirements of the project, e.g., FDA pre-submission meeting(s), submission for an IDE?

    UH3 Phase:

    • Are adequate quantitative milestones included for key stages of the clinical study?
    • Is a reasonable patient engagement timeline included for major activities to be performed with or by patients, e.g., patient enrollment, implants, assessments, data collection?
    • Do the milestones include clear go/no-go points for evaluation of device safety and efficacy?
    • Are the outcome metrics of the proposed clinical study quantifiable in terms of minimum success criteria? Is the next step in technology translation articulated, and will the clinical study outcome metrics enable that next step?

    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)?

    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

    Vertebrate Animals

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

    Biohazards

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

    Resubmissions

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

    Renewals

    Not Applicable

    Revisions

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

    Additional Review Considerations

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

    Intellectual Property (IP) strategy (attachment):

    • 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?
    • If multiple institutions/companies are involved, is IP sharing addressed?

    Applications from Foreign Organizations

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

    Select Agent Research

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

    Authentication of Key Biological and/or Chemical Resources:

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

    Budget and Period of Support

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

    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 will receive a written critique.

    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.

    Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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 recipient's business official.

    Recipients 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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

    Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient 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).

    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, Recipients, 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

    HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

    Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

    Cooperative Agreement Terms and Conditions of Award

    The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75,, 2 CFR Part 200 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 recipients 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 reside with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
    The PD(s)/PI(s) will have the primary responsibility for:

    • Defining objectives and approaches, and 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.
    • Working closely with his/her institution's technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner.
    • Providing progress reports with a 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, recipients agree to provide the data.
    • Participate in progress meetings (virtual) at least twice a year that are organized with 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 providing IDE/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 study is performed in accordance with Good Clinical Practices (GCP) and all IC-specific guidelines for data and safety monitoring in clinical trials (https://grants.nih.gov/policy/humansubjects/policies-and-regulations/data-safety.htm), and must provide data and regular updates to NIH
    • Presenting project updates (including raw data, when requested) in conference calls and annual face-to-face meetings of the BPMT External Oversight Committee in the Washington, DC area.
    • Collaborating and communicating effectively with NIH service contractors to achieve project goals

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

    • The Project Coordinator will have substantial programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond the levels required normally for program stewardship of grants, as described below.
    • Each project will have the support of one or more Subject Matter Expert(s) from NIH program staff who are consulted based on their expertise in the disorder(s) being studied and / or the implementation of the proposed translational research.
    • NIH program staff may 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 program staff provide input on the milestones and make recommendations regarding their finalization.
    • NIH program staff will be responsible for assessing the project's progress towards the specified milestones and recommending if further funds should be released to the project.
    • NIH program staff, in consultation with the PIs, may in rare occasions add critical 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 from NIH.
    • NIH program staff participate in meetings together with PIs with regulatory agencies related to the funded project.
    • NIH program staff may consult as necessary with independent consultants or specialists with relevant expertise.
    • A Blueprint MedTech Program Director may be assigned to an award with the primary responsibility for the overall coordination of research efforts across different funding mechanisms and research activities.
    • On rare, well-justified occasions, future-year milestones may be renegotiated 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.
    • The leadership of the Institute/Center funding the project will make decisions on project continuation, in coordination with Blueprint MedTech staff, NIH staff, and the External Oversight Committee, based on:
      • Successful achievement of milestones
      • The overall feasibility of project advancement, considering data that may not have been captured in milestones
      • The competitive landscape for the disease indication and technology
      • Program priorities
      • Availability of Blueprint MedTech resources
      • Availability of funds
    • This second level of approval is designed to mitigate any potential perceived bias in the administration of the cooperative agreement. If there is a disagreement on the recommendation for project continuation, concerns may be escalated to the Blueprint Institute Directors for a final decision.

    Collaborative Responsibilities:

    • Clarifying and negotiating the milestones and timelines.
    • Coordination of site visits, if needed, at critical milestones or transition points of the award

    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 recipient This special dispute resolution procedure does not alter the recipient'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, recipients 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 RPPR, invention statement, and the expenditure data portion of the Federal Financial Report 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 recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

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

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

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

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

    Scientific/Research Contact(s)

    Nick Langhals, PhD

    National Institute of Neurological Disorders and Stroke (NINDS)

    Telephone: 301-496-1779

    Email: NINDS-Devices@nih.gov

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

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

    Melissa M Ghim, PhD
    National Institute Of Dental & Craniofacial Research (NIDCR)
    Phone: none
    E-mail: ghimm@mail.nih.gov

    Yuan Luo, Ph. D.
    National Institute on Aging (NIA)
    Phone: 301-496-9350
    Email: yuan.luo@nih.gov

    Leonardo Angelone, Ph.D
    National Institute on Drug Abuse (NIDA)
    Email: Blueprint-MedTech@nih.gov

    Stacie Gutowski, PhD
    National Institute on Drug Abuse (NIDA)
    Email: Blueprint-MedTech@nih.gov

    Thomas Greenwell
    National Eye Institute (NEI)
    Phone: 301-443-5405
    E-mail: greenwellt@mail.nih.gov

    Michael Wolfson
    National Institute Of Biomedical Imaging And Bioengineering (NIBIB)
    Phone: 301-451-4778
    E-mail: michael.wolfson@nih.gov

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

    Elizabeth Powell
    National Institute On Alcohol Abuse And Alcoholism (NIAAA)
    Phone: 301-443-0786
    E-mail: elizabeth.powell3@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)

    Anna Taylor, PhD

    National Institute of Neurological Disorders and Stroke (NINDS)

    Telephone: 301-496-4245

    Email: Anna.Taylor@nih.gov

    Terri Jarosik
    National Institute of Mental Health (NIMH)
    Telephone: 301-443-3858
    Email: tjarosik@mail.nih.gov

    Shelley Headley
    National Center for Complementary and Integrative Health (NCCIH)
    Phone: 301-594-3788
    Email: shelley.headley@nih.gov

    Diana Rutberg, MBA
    National Institute Of Dental & Craniofacial Research (NIDCR)
    Phone: (301) 594-4798
    E-mail: dr258t@nih.gov

    Jill Morris
    National Institute on Aging (NIA)
    Phone: 301-496-8986
    Email: morrisjil@mail.nih.gov

    Pamela G Fleming
    National Institute On Drug Abuse (NIDA)
    Phone: 301-480-1159
    E-mail: pfleming@mail.nih.gov

    Karen Robinsonsmith
    National Eye Institute (NEI)
    Phone: (301) 451-2020
    E-mail: kyr@nei.nih.gov

    Margaret Young
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-642-4552
    Email: margaret.young@nih.gov

    Judy Fox
    National Institute On Alcohol Abuse And Alcoholism (NIAAA)
    Phone: (301) 443-4704
    E-mail: jfox@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 2 CFR Part 200, 42 CFR Part 52 and 45 CFR Part 75.


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