Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

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

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.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Blueprint MedTech

The NIH Blueprint for Neuroscience Research is a collaborative framework through which 12 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 several challenges along the translational path from bench to bedside. The Blueprint MedTech program aims to address such challenges and support the innovators by accelerating the development of medical devices to prevent, monitor, diagnose, and treat disorders within the missions of the participating NIH institutes and centers, as well as the HEAL and BRAIN Initiatives. The mission of the program is to catalyze the translation of novel technologies from early-stage development towards 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 NIH-funded translational services and contract research organizations  (e.g., design and prototyping, bench testing, large animal testing, biocompatibility assessment, manufacturing, medical monitoring, clinical trials).
• Assistance from NIH-funded service providers (e.g., on regulatory, reimbursement, intellectual property, commercialization, and strategic partnership issues).
• Advice from industry experts (e.g. mentors, 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 Notice of Funding Opportunity (NOFO) is to support investigators in pursuing translational activities and clinical studies to advance the development of therapeutic and diagnostic devices for disorders within the missions of the participating NIH institutes and centers, as well as the HEAL and BRAIN Initiatives. Activities supported by this NOFO 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 subsequent clinical study, feasibility, or pivotal clinical trial as appropriate. 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. Check the relevant institute interest statements and websites for additional limitations on clinical study requirements and limitations.

All projects must have two phases: UG3 and UH3. The UG3 phase will support translational device activities 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 with a UG3 phase. The duration of the UG3 phase will depend on the maturity of the project at entry, and the specific indication, and can range from one to four years. Only those UG3 phase projects that have met specific criteria (see below) will be eligible for transition to the UH3 phase after NIH administrative review. The UH3 phase will support a clinical study and can last up to four years. The total proposed project period (including both the UG3 and UH3 phases) may be up to five years. 

This NOFO utilizes a UG3/UH3 cooperative agreement funding mechanism. As a cooperative agreement, this NOFO supports milestone-driven projects and involves NIH program staff’s participation in negotiating project and milestone 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.

B. Scope
Projects must focus on a disease or disorder that falls within the mission of participating Institutes and Centers, as well as the HEAL and BRAIN Initiatives. It is expected that devices within the scope of this program either:

• are very close to the 'final system' and manufactured using very close to the same manufacturing process as the device to be marketed or studied in a larger clinical trial following the completion of this project; or
• have received Pre-Submission feedback from the FDA (see FDA/CDRH Q-Submission website and CDRH-learn website additional resources); or
• require early feasibility clinical data to inform the final device design or manufacturing processes.

C. Entry criteria
Applicants to the Blueprint MedTech program must include novel medical device technologies in the proposal that will advance patient care towards new or improved therapeutics or diagnostics that are safe and effective.

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, new safety questions, and/or new regulatory questions. Responsive applications may also 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.

It is recommended that applicants reach out to the NIH program staff listed  for this funding opportunity to discuss mission fit with respect to proposed technologies and indications as well as additional IC-specific requirements. https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-medtech/blueprint-medtech-ics-and-contacts

For entry to the program, projects should have:

• Comprehensive supporting data based on bench, in vitro, and/or in vivo models that are 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 by the end of the UG3 phase.

Applicants are encouraged, but not required, to consult with FDA via a Pre-Submission meeting. 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 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 (cGMP) 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, Breakthrough Device Designation).
• Use of the clinical experience to inform device design decisions.

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 may be proposed during the UH3 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;
• 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;
• Projects focused on technologies for augmentation of healthy individuals;
• Delayed-onset clinical studies;
• Device technologies not regulated by the FDA.

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

• Specific Aims that cover activities for both UG3 and UH3 phases of the award
• A delayed-start (not delayed onset) clinical study or trial planned in the UH3 phase, including all required documentation to support the study.

Applications that do not include the following required attachments or are over the specified page limits will also be considered incomplete and/or non-compliant and will be withdrawn and not reviewed:

• The following other attachments:
  • Needs Assessment (3 pages max),
  • IP Strategy (3 pages max),
  • Gantt Chart (1 page max),
  • Long-term care plan (3 pages max),
  • Resource Checklist (3 pages max)
• UG3 and UH3 milestone plans
• Team management plan (2 pages max)

Applications that include the following optional attachments, but are over the specified page limits will also be considered non-compliant and will be withdrawn and not reviewed:

• The following optional other attachments:
  • Schematics (2 pages max),
  • IRB Communications (5 pages max),
  • FDA Communications (10 pages max including summary)

Review the relevant institute interest statements for your proposed submission and contact the program staff listed in the link to discuss your proposal, clinical study requirements, and additional budget considerations prior to submission.
https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-medtech/blueprint-medtech-ics-and-contacts

F. Milestones
Because device development is an inherently risky process, it is anticipated that there may be attrition as projects progress. As stated by the SF424 (R&R) Application Guide, Specific Aims are goals, specific objectives, and expected outcomes of the proposed research. These Specific Aims are the activities that enable a company to reach a milestone, i.e., important decision points at which significant uncertainty for the project is resolved (go / no-go decision point). Each Specific Aim in the application should therefore have at least one milestone associated with it. Moreover, each milestone should be tied to tangible deliverables that are specific, measurable, achievable, relevant, and time-bound. Because of the specific requirements of the program, applicants are recommended to include aims, milestones and associated deliverables addressing both technical and commercial feasibility.

Applicants are encouraged to read examples of milestones within IC-specific interest statements (https://neuroscienceblueprint.nih.gov/neurotherapeutics/blueprint-medtech/blueprint-medtech-ics-and-contacts).

NIH program staff will contact the applicant to discuss and negotiate the proposed milestones and any changes suggested prior to funding the application. The final agreed upon and approved milestones will be specified in the Notice of Award (NoA). Progress towards achievement of the final set of milestones will be evaluated 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 may be discontinued. In addition to milestones, the decision  regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, portfolio balance and program priorities, competitive landscape, and availability of funds.

UG3 phase to UH3 phase transition:

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

• Successful achievement of the defined milestones for the UG3 phase of the project;
• 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;
• 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 recipients 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 a UG3/UH3 cooperative agreement, NIH program staff will be involved in the negotiation and execution of the project. Applicants are strongly encouraged to consult with NIH program 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 the Blueprint MedTech website for specific IC requirements and interest statements.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

• 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 Organizations)

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; 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 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.

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 their organization to develop an application for 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 How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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:
Blueprint MedTech
Email: [email protected]

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- 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
• and identify significant issues faced by stakeholders (patients, clinicians, caregivers, customers), which is a key step in the design control process and will be evaluated for adequacy;
• critically evaluate primary or secondary data that have been used to identify deficiencies in current capabilities and the origins of the problem or critical barrier;
• describe the beneficiaries of the proposed work and how their needs have been identified;
• distinguish "wants" from "needs" and outline the involvement of those who will benefit in the development of a solution;
• describe how finite resources can best be deployed to develop and disseminate a feasible and applicable solution; and
• identify any human factors (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 post-trial 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 lacking 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 - 3 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 recipients by providing prototype development, 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:

• Design Optimization and Clinical Prototype Manufacturing
• Bench and Safety Testing
• Biocompatibility and Animal Studies
• Clinical Support
• Business Development
• Regulatory, Compliance, and Quality Systems
• Legal
• Consultants

Applicants are 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 a description of the specific activities to be included for each requested resource, if known, as well as a justification for why any of the above activities are not being utilized in the current application.

Applicants are furthermore encouraged to visit Blueprint MedTech Resources and Support Services for detailed examples of offered resources.

Schematics (Optional – 2 pages 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.

IRB Communications (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 How to Apply- Application Guide must be followed.

R&R Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- 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 covering the UG3 and UH3 phases of the award.

Research Strategy
The Research Strategy should include the following subsections:

Significance

A. Clinical Impact and Feasibility
Please note that each application must focus on a disease or disorder that falls within the mission of participating Institutes and Centers, even if the device proposed for development could be used for more than one. The target patient population and intended use should guide the design of the device and 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 efforts or significant efforts underway in academia and industry including agents, therapeutics, and devices.
• Describe 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 in vivo 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 and/or trial(s).
• A clear schematic, drawing, and/or image should be included along with the device description either in the supporting data section or as an optional attachment (see above, Other Attachments- Schematics).
• Applicants should justify the type of stimulation proposed, target(s), and patient population.
• Blinding, randomization, power analysis for sample size, and independent replication should be included in the application wherever possible.
• For applications proposing first-in-human studies, preliminary data in humans are not required.
• The application should present a credible path towards an IDE – for an SR study - or IRB approval – for an NSR 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 – for SR studies – or IRB approval  for an NSR 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 pre-submission meetings or IDE submission), if available, should indicate that the regulatory path to market is reasonable;
• A description of what methods, procedures, and/or 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.

UG3 phase: 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 – for SR study - or to IRB approval - for an NSR 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)).
• Plans for contact with and submissions to the FDA (e.g., pre-submission meetings and/or IDE submission).
• Plans for all necessary benchtop and animal studies required by the FDA. 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.
• Plan for possible minor alterations to the device design, if 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.
• Plan for testing acceptability, feasibility and integration into user and customer workflow, depending on specific indication (hospital setting, home setting)
• Provide a compelling justification for developing the proposed product regarding potential advances in clinical practice, public health, and patient quality of life.
• Describe the team's expertise in the technical, commercial, and clinical areas relevant to the proposed project.

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 and associated deliverables should address both technical, regulatory, and commercial feasibility.
• Milestones should include planned interactions with the FDA to obtain feedback regarding the specific regulatory pathway, the required preclinical testing (e.g., benchtop testing, animal studies, biocompatibility studies, where applicable), and the planned Phase II clinical study. Additionally, milestones should clearly include a plan to obtain an FDA IDE approval – for SR study – or IRB approval – for NSR 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, should be included 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) must 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 (generally 2 pages max).

 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

Data Management and Sharing Plan - Required

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• If patent protection is being sought, investigators should explain how data will be shared after filing for patent protection to allow for both further research and the development of commercial products to advance forward, consistent with achieving the goals of the program.

Use of Common Data Elements in NIH-funded Research

The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.

• Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014)
• Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
• NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
• NIH encourages human-subject studies to incorporate the measures from the Core and Specialty collections, which are now available in the PhenX Toolkit (www.phenxtoolkit.org) (for example, see NOT-DA-12-008, NOT-MH-15-009)
• Data should be organized according to a standard model that is widely accepted within the field. An example for the clinical research studies would be the OMOP Common Data Model, which has also been successfully adapted for use with observational (including survey) studies more generally. In addition, the HL7 FHIR (Fast Healthcare Interoperability Resources) standard (NOT-OD-19-122) may facilitate the flow of data with electronic health record (EHR)-based datasets, tools, and applications.
• NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.

Recipients conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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 How to Apply- 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 How to Apply- 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). Applications that lack a UH3 Milestone Plan are considered incomplete / non-responsive and will not be peer reviewed. Both milestone plans will be negotiated prior to issuing the notice of award for each phase.

• 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.
• 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:

• Registration of clinical trial in ClinicalTrials.gov;
• Completion of additional 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;
• Other protocol-specific performance milestones and timeline

Section 3 - Protection and Monitoring Plans
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 addressing the guiding principles (see Neuroethics Guiding Principles for the NIH BRAIN Initiative for additional considerations).

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 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. An organizational structure that clearly defines the team structure and relationships among the various components should 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.

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 (Optional - 10 pages max including summary):

• Applicants should include a summary (1 page max of the 10 pages total) of interactions with the FDA, supported by the following associated documentation most pertinent for justifying the project development plan: 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 How to Apply- Application Guide must be followed.

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

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described 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 the 10 pages total) of interactions with the FDA, supported by the following associated and attached documentation most pertinent for justifying the project development plan:

• 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.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

Specific to this NOFO:

• Evaluate the following based on information provided in Intellectual Property (IP) Strategy attachment:
  • Evaluate whether potential issues regarding the IP landscape for the device being developed and means for addressing any IP hurdles/barriers are addressed and whether the IP Strategy attachment and related letters of support address potential concerns.
  • Assess if there are any known constraints that could impede the development of the device.
  • Evaluate whether IP filing plans are well described and appropriate.
  • If multiple institutions/companies are involved, evaluate whether IP sharing is adequately addressed.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) in accordance with NIH peer review policies and practices, 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 committee 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 NOFO. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

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 (HHS) grant administration regulations at 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 recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Defining objectives and approaches, and for planning, conducting, analyzing, interpreting, drawing conclusions on their studies, publishing, and sharing the results.
• Developing and proposing rigorous milestones that will be achieved during the project period.
• Retaining custody of and have all rights to the data and technology developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Pursuing patent protection, as appropriate and consistent with the terms and conditions of the award and goals of the program.
• Providing progress reports with 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 to provide 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 (e.g. NINDS Guidelines for Monitoring in Clinical Trials), and must provide data and regular updates to NIH.
• 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 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. The responsibility of the SME is to advise the Program Official on project approvals.
• NIH program staff provide input on the milestones and make recommendations regarding their finalization.
• NIH program staff will be responsible for assessing the progress of the project towards the specified milestones, and for recommending if further funds should be released to the project.
• NIH 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 some 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, assuming confidentiality agreements are in place to mitigate conflicts and protect intellectual property.
• An NIH 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.
• In 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.
• In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NIH portfolio balance and program priorities, competitive landscape, and availability of funds.
• The Program Officer will  be responsible for normal programmatic stewardship and be listed on the NoA. However, the Associate Division Director overseeing this program will make final decisions on project continuation based on program staff recommendations, programmatic prioritization, and budget considerations. 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 between program staff and the Associate Division Director, they will collaborate with the other Associate Division Directors for resolution of the disagreement with program officials. If disagreements remain, concerns may be escalated to the Director of the Institute for final decision.

Areas of Joint Responsibility include:

• None; all responsibilities are divided between recipients and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual 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 HHS regulation 45 CFR Part 16. Final decisions made by NIH regarding a discontinuation are not appealable.

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. 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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

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: https://www.era.nih.gov/need-help (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: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Nick Langhals, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: [email protected]

Leonardo Angelone, PhD
National Institute on Drug Abuse (NIDA)
Email: [email protected]

Erin Burke Quinlan, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: (301) 451-0636
Email: [email protected]

Tony Douglas Gover
NEI - NATIONAL EYE INSTITUTE
Phone: 301-529-7370
E-mail: [email protected]

Paekgyu Lee
NEI - NATIONAL EYE INSTITUTE
Phone: (301) 435-8164
E-mail: [email protected]

Elizabeth Powell, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0786
Email: [email protected]

Eunyoung Kim, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-496-3513
Email: [email protected]

Michael Wolfson
NIBIB - NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
Phone: 301-451-4778
E-mail: [email protected]

Melissa M Ghim, PhD
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: none
E-mail: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Amy Connolly
National Institute on Drug Abuse (NIDA)
Email: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

Karen Robinson Smith
NEI - NATIONAL EYE INSTITUTE
Phone: 301-435-8178
E-mail: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

Gabriel Hidalgo, MBA
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-827-4630
E-mail: [email protected]

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.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.