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)

Funding Opportunity Title
Translational Neural Devices (U44 Clinical Trial Optional)
Activity Code

U44 Small Business Innovation Research (SBIR) Cooperative Agreements - Fast-Track

Announcement Type

Reissue of RFA-NS-18-012 -Translational Neural Devices (U44  Clinical Trial Required)

Related Notices
Funding Opportunity Announcement (FOA) Number
RFA-NS-21-022
Companion Funding Opportunity

RFA-NS-21-021 - Translational Neural Devices (UG3/UH3 Clinical Trial Optional)

Assistance Listing Number

93.853

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications from Small Business Concerns (SBCs) to pursue translational activities and small clinical 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 leading to submission of an Investigational Device Exemption (IDE) to the U.S. Food and Drug Administration (FDA) or Institutional Review Board (IRB) application for a Non-Significant Risk (NSR) 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.

Key Dates

Posted Date
April 28, 2021
Open Date (Earliest Submission Date)
June 01, 2021
Letter of Intent Due Date(s)

60 days prior to the receipt date.

Application Due Date(s)

July 1, 2021;October 20, 2021; February 18, 2022; June 20, 2022; October 18, 2022; February 21, 2023; June 19, 2023; October 18, 2023; February 20, 2024

 

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

November 2021, March 2022, July 2022, November 2022, March 2023, July 2023, November 2023, March 2024, July 2024

Advisory Council Review

January 2022, May 2022, October 2022, January 2023, May 2023, October 2023, January 2024, May 2024, October 2024

Earliest Start Date

March 2022; July 2022; November 2022; March 2023; July 2023; November 2023; March 2024; July 2024; November 2024

Expiration Date
February 21, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the SBIR/STTR (B) Instructions in  the SF424 (R&R) SBIR/STTR Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

A. Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage investigators to pursue translational activities and small clinical 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 small clinical 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.

B. Overview

This FOA supports non-clinical testing to enable IRB and/or FDA approval needed to conduct a small clinical study, and the subsequent study itself (e.g., Early Feasibility Study - https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm279103). All projects will be Fast-Track applications and have two phases. SBIR Phase I will support non-clinical 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. The duration of SBIR Phase I will depend on the maturity of the project at entry. Phase II will support a small clinical study and can last up to three years, however, the total project period (including both phases) must not exceed five years. Projects for which only a clinical phase is proposed are outside of the scope of this funding opportunity. Only those SBIR Phase I projects that have met specific criteria (see below) will be eligible for transition to SBIR Phase II after NIH administrative review. Furthermore, ethical considerations are intrinsic to the responsible conduct of neuroscience research and the translation of neuroscience advances (scientific and technological) into clinical practice. It is expected the immediate next steps following completion of the small clinical study supported under this cooperative agreement will be:

  • a marketing application if only a small clinical study or experience is needed to demonstrate the device is safe and effective.
  • a larger clinical trial that will lead to a marketing application; or
  • device design decisions made based on the information and data collected.

As applicants must have comprehensive supporting data, innovation and impact will in part be judged on presenting a credible path towards U.S. regulatory submission/IRB approval at the end of the SBIR Phase I project period, and on the potential to advance the care of patients by addressing an unmet clinical need.

This FOA will utilize a Small Business Innovation Research (SBIR) U44 cooperative agreement. As a cooperative agreement, this FOA 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.

Applicants are strongly advised to contact the Scientific/Research contact listed below prior to submission.

C. Scope

Projects must focus on a disorder that falls within the mission of NINDS. It is expected that devices within the scope of this program either:

D. Entry criteria:

For entry to the program, projects should have:

  • Comprehensive supporting data based on bench, in vitro, and/or in vivo models representative of the intended patient population and indication.
  • Identified one or more clinically meaningful device outcome measures based on input from 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 at the end of SBIR Phase I. All regulatory approvals must be in place prior to the start of the SBIR Phase II.

Applicants are encouraged, but not required, to consult with FDA via a Pre-Submission meeting, study risk designation request, and/or 513(g) submission prior to applying for funding through this grant mechanism. Applicants who do not have sufficiently relevant feedback from the FDA regarding all planned activities prior to application for funding will be expected to do so as the first milestone during the first year of SBIR Phase I of the award. Funding will be restricted to a maximum of $100,000 in direct costs until FDA feedback that is consistent with the likely success of the regulatory path to market and overall device development plan outlined in the grant application is received. In the event that FDA feedback is not consistent with the plans in the grant, program staff will evaluate the concerns and change of scope that would be needed and work with the investigators to determine the most appropriate course of action. Any remaining funds associated with the original award will not be released.

E. Phases

SBIR Phase I scope:

Examples of studies that may be proposed during SBIR Phase I 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,
  • Device, software, and firmware design verification and validation activities.
  • Development of packaging, connectors, and other accessories necessary for the translation of this technology.
  • Regulatory activities, including pre-submission meetings with FDA, IDE submission, or other FDA regulatory submissions (e.g., Humanitarian Device Exemption (HED), Request for Risk Designation, 513(g) submission).
  • A limited clinical experience is also allowable during SBIR Phase I if it is necessary to support the IDE submission for the small clinical study conducted in SBIR Phase II. Clinical studies in SBIR Phase I are out of scope if the planned SBIR Phase II small clinical study is NSR.

SBIR Phase II scope:

SBIR Phase II will support a small clinical study that will lead to either:

  • A marketing application if only a small clinical trial or experience is needed to demonstrate the device is safe and effective, or
  • A larger clinical trial that will lead to a marketing application; 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 SBIR Phase II 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.
  • Basic proof-of-concept testing in human patients.
  • 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

F. Non-Responsive Activities: Applications that include the following activities will be considered non-responsive and will be withdrawn and not reviewed:

  • Basic research and studies of disease mechanisms;
  • Animal model development: all in vivo models must be well 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 are outside the scope of the present FOA;
  • Delayed onset clinical studies
  • Proposals lacking a clinical study protocol included with the submission
  • Projects focused on technologies for augmentation of healthy individuals
  • Applications that do not include all required attachments (e.g., Gantt Chart, Long-term care plan)
  • Applications that do not include a neuroethics section as part of the human subjects protection attachment.

G. Milestones

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

For each milestone, provide details on methods, assumptions, experimental designs, and data 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 (https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library/Devices-Milestones).

NIH program staff will contact the applicant to discuss, 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 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.

SBIR Phase I to Phase II transition:

An administrative review will be conducted by program staff, with potential input by independent consultants, to decide whether a SBIR Phase I project will be transitioned into SBIR Phase II based on the following:

  • Successful achievement of the defined milestones for SBIR Phase I of the project;
  • Likelihood of success in clinical testing;
  • Competitive landscape;
  • Program balance;
  • Availability of funds;
  • 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 humans subjects obtained from the NINDS Safety and Risk Assessment Committee (SARAC); and
  • Agreement on updated timeline, milestones and budget for the clinical study.

H. Quality and Compliance Requirements

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.

I. 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.

J. Pre-application Consultation

As an U44 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.

K. Institute Statements of Interest

The National Institute for Neurological Disorders and Stroke (NINDS) will support translational device applications relevant to its mission (https://www.ninds.nih.gov/About-NINDS/Who-We-Are) under this FOA. Applications for NINDS proposing pre-translational, pre-clinical, investigative research projects on deliberative optimization and development of devices for impacts in neurology and neuroscience should apply through the Bioengineering Research Grants (R01s: see PAR-19-158 and PAR-19-159).

Applicants are expected to incorporate data elements from the NINDS Common Data Elements (CDE) Project in their data collection forms when appropriate (see https://www.commondataelements.ninds.nih.gov).

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
Revision
New (Fast-Track)
Resubmission (all phases)

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 the 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. NINDS anticipates funding 3-5 awards per fiscal year for $4,000,000.

Award Budget
Applicants should rarely exceed $1,000,000 in total costs per year during the SBIR Phase I and $1,500,000 in total costs per year during the SBIR Phase II.

Award Project Period

SBIR Phase I can last up to 2 years.

SBIR Phase II can last up to 3 years.

The total duration of both Phase I and Phase II must 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

Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity. A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria:

  1. Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;
  2. Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there must be less than 50 percent participation by foreign business entities in the joint venture;
  3.  
    1. SBIR and STTR.  Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), an Indian tribe, ANC or NHO (or a wholly owned business entity of such tribe, ANC or NHO), or any combination of these; OR
    2. SBIR-only.  Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these.  No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern, unless that single venture capital operating company, hedge fund, or private equity firm qualifies as a small business concern that is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States; OR
    3. SBIR and STTR.  Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with § 121.705(b) concerning registration and proposal requirements.
  4. Has, including its affiliates, not more than 500 employees.

    If the concern is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these falls under 3 (ii) or 3 (iii) above, see Section IV. Application and Submission Information for additional instructions regarding required application certification.

    If an Employee Stock Ownership Plan owns all or part of the concern, each stock trustee and plan member is considered an owner.

    If a trust owns all or part of the concern, each trustee and trust beneficiary is considered an owner.

    Definitions:

  • Hedge fund has the meaning given that term in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The hedge fund must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
  • Portfolio company means any company that is owned in whole or part by a venture capital operating company, hedge fund, or private equity firm.
  • Private equity firm has the meaning given the term “private equity fund” in section 13(h)(2) of the Bank Holding Company Act of 1956 (12 U.S.C. 1851(h)(2)). The private equity firm must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
  • Venture capital operating company means an entity described in § 121.103(b)(5)(i), (v), or (vi). The venture capital operating company must have a place of business located in the United States and be created or organized in the United States, or under the law of the United States or of any State.
  • ANC means Alaska Native Corporation.
  • NHO means Native Hawaiian Organization.

SBCs must also meet the other regulatory requirements found in 13 C.F.R. Part 121. Business concerns, other than investment companies licensed, or state development companies qualifying under the Small Business Investment Act of 1958, 15 U.S.C. 661, et seq., are affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both. Business concerns include, but are not limited to, any individual (sole proprietorship) partnership, corporation, joint venture, association, or cooperative. The SF424 (R&R) SBIR/STTR Application Guide should be referenced for detailed eligibility information.

Small business concerns that are more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these are NOT eligible to apply to the NIH STTR program.

Phase I to Phase II Transition Rate Benchmark

In accordance with guidance from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of 2011.   This Transition Rate requirement applies to SBIR and STTR Phase I applicants that have received more than 20 Phase I awards over the past 5 fiscal years, excluding the most recently-completed fiscal year.  For these companies, the benchmark establishes a minimum number of Phase II awards the company must have received for a given number of Phase I awards received during the 5-year time period in order to be eligible to apply for a new Phase I award Fast-Track, or Direct Phase II (if available).  This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5 year period. 

Companies that do not meet or exceed the benchmark rate will not be eligible to apply for a Phase I Fast-Track, or Direct Phase II (if available) award for a period of one year from the date of the application submission.  The Transition Rate is calculated as the total number of SBIR and STTR Phase II awards a company received during the past 5 fiscal years divided by the total number of SBIR and STTR Phase I awards it received during the past 5 fiscal years excluding the most recently-completed year.  The benchmark minimum Transition Rate is 0.25.   

SBA calculates individual company Phase I to Phase II Transition Rates daily using SBIR and STTR award information across all federal agencies.  For those companies that have received more than 20 Phase I awards over the past 5 years, SBA posts the company transition rates on the Company Registry at SBIR.gov.   Information on the Phase I to Phase II Transition Rate requirement is available at SBIR.gov. 

Applicants to this FOA that may have received more than 20 Phase I awards across all federal SBIR/STTR agencies over the past five (5) years should, prior to application preparation, verify that their company’s Transition Rate on the Company Registry at SBIR.gov meets or exceeds the minimum benchmark rate of 0.25. 

Phase II to Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including NIH, SBIR/STTR Programs are implementing the Phase II to Commercialization Rate benchmark for Phase I applicants, as required by the SBIR/STTR Reauthorization Act of 2011. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537).

This requirement applies to companies that have received more than 15 Phase II awards from all agencies over the past 10 years, excluding the two most recently-completed Fiscal Years. Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0.15 (15%) patents per Phase II award resulting from these awards. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10 year period, excluding the two most recently-completed Fiscal Years.

Information on the Phase II to Commercialization Benchmark is available at SBIR.gov. 

Applicants to this FOA that may have received more than 15 Phase II awards across all federal SBIR/STTR agencies over the past ten (10) years should, prior to application preparation, verify that their company’s Commercialization Benchmark on the Company Registry at SBIR.gov meets or exceeds the benchmark rate listed above.

Applicants that fail this benchmark will be notified by SBA annually and will not be eligible to apply for New Phase I, Fast-track or Direct Phase II (if applicable) awards for a period of one year. 

Foreign Institutions

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

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, may be 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, SBA Company registry, 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.
  • SBA Company Registry –See Section IV. Application and Submission Information, “SF424(R&R) Other Project Information Component” for instructions on how to register and how to attach proof of registration to your application package.  Applicants must have a DUNS number to complete this registration.  SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
  • eRA Commons - Applicants must have an active DUNS number 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.

Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PDs/PIs, at least one must meet the primary employment requirement. Occasionally, deviations from this requirement may occur.

For the STTR program, the PD(s)/PI(s) may be employed with the SBC or the single, “partnering” non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration The primary employment of the PD/PI must be with the SBC or the Research Institution (where they are PD/PI at) at the time of award and during the conduct of the proposed project.

 

Each PD/PI must commit a minimum of 10% effort to the project.

The SF424 (R&R) SBIR/STTR Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the SF424 (R&R) SBIR/STTR 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.

NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process, or service that, with non-substantive modifications, can be applied to a variety of purposes. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and any other HHS funding opportunity, including the SBIR and STTR Parent announcements.

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).

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II or IIB support, a Phase I awardee should submit a Phase II application, and a Phase II awardee should submit a Phase IIB application, within the first six due dates following the expiration of the Phase I or II budget period, respectively.

Contractual/Consortium Arrangements

In Phase I, normally, two-thirds or 67% of the research or analytical effort is carried out by the small business concern. The total amount of all consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 33% of the total amount requested (direct, F&A/indirect, and fee).

In Phase II, normally, one-half or 50% of the research or analytical effort is carried out by the small business concern. The total amount of consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

We encourage you to contact a program officer listed in Section VII with questions about this because occasionally, deviations from these requirements may occur, and must be approved in writing by the funding agreement officer after consultation with the agency SBIR Program Manager/Coordinator. The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct, F&A/indirect costs, and fee attributable to each party, unless otherwise described and justified in “Consortium/Contractual Arrangements” of the PHS 398 Research Plan component of the SF424 (R&R) application forms.

 

A small business concern may subcontract a portion of its SBIR or STTR award to a Federal laboratory within the limits above.  A Federal laboratory, as defined in 15 U.S.C. § 3703, means any laboratory, any federally funded research and development center, or any center established under 15 U.S.C. §§ 3705 & 3707 that is owned, leased, or otherwise used by a Federal agency and funded by the Federal Government, whether operated by the Government or by a contractor.

 

The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in “Consortium/Contractual Arrangements” of the PHS 398 Research Plan component of SF424 (R&R) application forms.

 

Additional details are contained in the SF424 (R&R) SBIR/STTR Application Guide.

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 SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR 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:
Eric Hudak, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: NINDS-Devices@nih.gov 

Page Limitations

All page limitations described in the SF424 (R&R) SBIR/STTR 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) SBIR/STTR Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments:

1. SBIR Application Certification for small business concerns majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms

Applicant small business concerns that are majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms (e.g. majority VCOC-owned) are required to submit a Certification at time of their application submission per the SBIR Policy Directive.  Follow the instructions below. 

Applicants small business concerns who are more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these (i.e. NOT majority VCOC-owned) should NOT fill out this certification and should NOT attach it their application package.

  1. Download the “VCOC Certification.pdf” at the NIH SBIR Forms webpage. 
  1. Answer the 3 questions and check the certification boxes.
  1. The authorized business official must sign the certification.
  1. Save the certification using the original file name.  The file must be named “SBIR Application VCOC Certification.pdf”.  DO NOT CHANGE OR ALTER THE FILE NAME.  Changing the file name may cause delays in the processing of your application.
  1. When you are completing the application package, attach this certification as a separate file by clicking "Add Attachments" located to the right of Other Attachments field on the “Research and Related Other Project Information” form.

Commercialization Plan

Applicants must follow the requirements outlined in the application guide: (https://grants.nih.gov/grants/how-to-apply-application-guide/forms-f/general/g.440-sbir-sttr-information-form.htm), including the following sections:

  • Value of the SBIR/STTR Project, Expected Outcomes, and Impact
  • Company
  • Market, Customer, and Competition
  • Intellectual Property (IP) Protection
  • Finance Plan
  • Production and Marketing Plan
  • Revenue Stream

SBA Company registry

All applicants to the SBIR and STTR programs are required to register at the SBA Company Registry prior to application submission and attach proof of registration. Completed registrations will receive a unique SBC Control ID and .pdf file. If applicants have previously registered, you are still required to attach proof of registration. The SBA Company Registry recommends verification with SAM, but a SAM account is not required to complete the registration. In order to be verified with SAM, your email address must match one of the contacts in SAM. If you are unsure what is listed in SAM for your company, you may verify the information on the SAM site. Confirmation of your company's DUNS is necessary to verify your email address in SAM. Follow these steps listed below to register and attach proof of registration to your application.

  1. Navigate to the SBA Company Registry.
  2. If you are a previous SBIR/STTR awardee from any agency, search for your small business by Company Name, EIN/Tax ID, DUNS, or Existing SBIR/STTR Contract/Grant Number in the search fields provided. Identify your company and click “Proceed to Registration”.
  3. If you are a first time applicant, click the "New to the SBIR Program?" link on lower right of registry screen.
  4. Fill out the required information on the “Basic Information” and “Eligibility Statement” screens.
  5. Press “Complete Registration” on the lower right of the “Eligibility Statement” screen and follow all instructions.
  6. Download and save your SBA registry PDF locally. The name will be in the format of SBC_123456789.pdf, where SBC_123456789 (9 digit number) is your firm’s SBC Control ID. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.
  7. When you are completing the application package, attach this SBA registry PDF as a separate file by clicking "Add Attachments" located to the right of the Other Attachments field on the “Research and Related Other Project Information” form

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.

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 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).

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 Expanded

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims

Include aims delineated for the non-clinical testing and the clinical study.

  • Define the aims of the SBIR Phase I non-clinical development of the device
  • Define the aims of the SBIR Phase II clinical trial
  • A scientific hypothesis is not required nor expected for work of this nature.

Research Strategy

The Research Strategy section should 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 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 either in the supporting data section or as an optional attachment (see above, Other Attachments- Schematics).
  • Applicants should justify the type of stimulation proposed (if applicable), 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 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 (SBIR Phase II) should be included in the PHS Human Subjects and Clinical Trials Information form.

SBIR Phase I: Non-clinical activities in SBIR Phase I 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 appropriate U.S. regulatory bodies (e.g., FDA in the form of pre-submission meetings and IDE submission), if applicable.
  • Plans for all necessary benchtop and animal studies required by the FDA to support an IDE. 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 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:

Milestones should be associated with clear, quantitative criteria for measuring success and efficacy that can be used for go/no-go decision making

SBIR Phase I

  • 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 trial, at a minimum, an FDA pre-submission meeting, with NIH program staff in attendance, is required as a Year 1 milestone. If the need for additional pre-submission meetings is anticipated, they should also include NIH program staff and should be included as milestones. Non-binding FDA feedback during and after this meeting must clearly indicate that the proposed non-clinical testing plan is sufficient to support a successful FDA submission for an IDE by the end of the non-clinical 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

SBIR Phase II:

  • Information related to human subjects and clinical studies that supports the SBIR Phase II 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 a letter of support from consultants, contractors, and collaborators.

  • If applying from an academic institution, include a letter of support from the technology transfer official who will be managing 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), 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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, must include a Data Sharing Plan

  • Investigators must follow the guidelines outlined in NOT-MH-19-010 when creating the data 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.
  • The plan should include information on IRB compliance for sharing de-identified data to maximize dissemination.
  • Applicants should anticipate that, if awarded, their project will join a consortium work group, coordinated by the NIH, to identify consensus standards of practice as well as supplemental opportunities to collect and provide data for ancillary studies, and to aggregate and standardize data for dissemination among the wider scientific community. Accordingly, the Data Sharing Plan should include a statement of agreement to join and cooperate with a future collaborative consortium of awardees to maximize data sharing opportunities (including collection, curation, analysis, and sharing) for this unique population of human subjects. The Data Sharing Plan should include accommodations for research-community input, including requests for collecting and disseminating data that will be valuable to the wider research community beyond the primary outcomes.

Appendix:

Note that Phase I SBIR/STTR Appendix materials are not permitted.  Only limited items are allowed in the Appendix of other small business applications.  The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide Instructions.

Please see NOT-OD-18-126 for allowable appendix materials

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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: 1 Phase II Milestone Plan: Applicants are required to provide detailed project performance and timeline objectives (note, Phase I 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 trial, especially participant recruitment, enrollment, and retention through the planned follow-up periods.
  • Yearly minimum success criteria for ongoing evaluations of device safety and efficacy that define clear go/no-go points should also be included as milestones.
  • 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 small clinical 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 (i.e.. patient enrollment, implants, assessments, data collection, etc.).

Examples of appropriate topics covered by SBIR Phase II Milestones include:

  • Finalization of clinical protocol (with program agreement, if applicable);
  • Registration of clinical trial in ClinicalTrials.gov;
  • Completion of regulatory approvals;
  • Enrollment of the first subject;
  • Enrollment and randomization, if applicable of the projected study population, including women, minorities and children (as appropriate);
  • Completion of 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 Plan

3.1 Protection of Human Subjects

In addition to the standard components, this section must include a Neuroethics section. Applications that lack a Neuroethics section are considered incomplete / non-responsive and will not be peer reviewed. Ethical considerations are intrinsic to the responsible conduct of neuroscience research and the translation of neuroscience advances (scientific and technological) into clinical practice. The NIH BRAIN Initiative emphasizes proactive, ongoing assessment of the neuroethical implications of the development and application of BRAIN-funded tools and neurotechnologies. 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, therapeutic misconception may be a concern, or for trials without a prospect of benefit to participants, the appropriateness of the risks of the study may require consideration) and
  • 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:

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.

Communications with FDA:

  • Applicants should include a summary (1-page max) of interactions with the FDA supported by the following documentation (10 pages maximum), which should be attached: approved minutes from all pre-submission meetings, notice of IDE approval and any associated attachments, risk determination, breakthrough device designation, 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.
  • 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) SBIR/STTR Application Guide must be followed.

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

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

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and time. 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) SBIR/STTR 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) SBIR/STTR 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.

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 (SAM). Additional information may be found in the SF424 (R&R) SBIR/STTR Application Guide.

See more tips for avoiding common errors.

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

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

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 U44 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? Does the proposed project have commercial potential to lead to a marketable product, process or service? (In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization?)

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 clearly described with sufficient detail, and does the device appear 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 SBIR Phase I? 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?

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?
  • Evaluate the Scientific Steering Group (SSG). Are the members appropriate? Has an interdisciplinary team been assembled?

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 identified? Are the changes in the proposed device likely to succeed where the predecessor did not?

In addition, for applications involving clinical trials

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

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? For a Phase I application, are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this announcement:

Overall Technology Translation Plan:

  • Are 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 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?

Detailed Plans for Research Strategy (Including Milestones and Timelines):

  • Will the implementation of the overarching plan lead to the development and testing of the proposed therapeutic device?
  • 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)?
  • Do the proposed project plan and timeline indicate a likelihood of reaching an IDE or IRB approval for a non-significant risk (NSR) study at end of the SBIR Phase I?

Long-term Patient Care:

  • 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? For example, does it address 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 lacking 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:

Study Design

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

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

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

Data Management and Statistical Analysis

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

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

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

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

Environment

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

Specific to this announcement

  • Is there sufficient regulatory expertise 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?

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.

Milestone Plan

  • Does the Gantt chart provide sufficient detail of the projected timeline with key project tasks? Do these details demonstrate feasible and well-justified plans 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 the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
  • Are there additional key experiments that need to have milestones?
  • Are milestones included that reflect the planned regulatory requirements of the project, e.g., FDA pre-submission meeting(s), submission for an IDE?

Commercialization Plan:

Market, Customer, and Competition:

  • How compelling is the value proposition, and to what extent does the application demonstrate a substantial market-pull for the technology under development?
  • How well has the applicant described the market niche(s) for the product/ technology, and how urgent is the unmet need(s) being addressed?
  • To what extent has the applicant identified realistic, market-based milestones that can be achieved over the next five years?
  • How well has the applicant demonstrated an understanding of the competitive environment in which they plan to sell their product?
  • To what extent has the applicant identified their customers and demonstrated a clear understanding of their needs?
  • How well has the company addressed potential hurdles that may delay or prevent acceptance of their product?
  • How reasonable are the applicant's plans for generating a revenue stream, and how realistic are the revenue projections?

Company:

  • How well can the applicant SBC sustain itself and grow as a business?
  • To what extent do the prior experience and qualifications of the project team members lend confidence that the team will be successful in commercializing the proposed product/technology? For example, how successful have the PD(s)/PI(s) been in commercializing other SBIR/STTR supported technologies and discoveries in the past?
  • To what extent will the applicant's business alliances and/or corporate partnerships help in facilitating commercialization? For example, will third-party investors play an active role in facilitating the commercialization of the product/technology, and if so to what extent?
  • If the SBC has received previous SBIR/STTR funding from ANY Federal agency, then how successful is the company’s track record in commercializing prior SBIR/STTR projects?

Intellectual Property (IP) strategy:

  • Are potential issues regarding the IP landscape for the device being developed and the freedom to operate 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?

Phase II Applications

For Phase II Applications, how well did the applicant demonstrate progress toward meeting the Phase I (or Phase I-like) objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

Phase I/Phase II Fast-Track Applications

For Phase I/Phase II Fast-Track Applications, reviewers will consider the following:

1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

2. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

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.

Phase IIB Competing 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.

Select Agent Research

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

Resource Sharing Plans

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

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 {LOCUS OF REVIEW}, 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.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDSC) Council. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

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

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.

Report fraud, waste and abuse

The Office of Inspector General Hotline accepts tips from all sources about potential fraud, waste, abuse and mismanagement in Department of Health & Human Services programs.  The reporting individual should indicate that the fraud, waste and/or abuse concerns an SBIR/STTR grant or contract, if relevant. Report Fraud.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies. The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the 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 resides 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 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 (see https://grants.nih.gov/grants/policy/nihgps/html5/section_8/8.2.4_inventions_and_patents.htm).
  • Providing progress reports with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not. In cases when NIH program staff request raw data, 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 Data and Safety Monitoring in Clinical Trials: http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm, and must provide data and regular updates to NIH

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

  • 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 Project Coordinator will also be responsible for normal programmatic stewardship as the Program Official. 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.

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

NIH requires that SBIR/STTR recipients submit the following reports within 120 days of the end of the grant budget period unless the recipient is under an extension. When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI.

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

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

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

SBA Company Registry (Questions regarding required registration at the SBA Company Registry and for technical questions or issues)
Website to Email: http://sbir.gov/feedback?type=reg

Scientific/Research Contact(s)

Eric Hudak, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: NINDS-Devices@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

Section VIII. Other Information

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

Authority and Regulations

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

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), as reauthorized and extended under P.L. 114-328, Section 1834, and P.L. 115-232. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.


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