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
NeuroNEXT Small Business Innovation in Clinical Trials (U44 Clinical Trial Optional)
Activity Code

U44 Small Business Innovation Research (SBIR) Cooperative Agreements - Fast track, Phase II

Announcement Type

Reissue of PAR-18-628 -NeuroNEXT Small Business Innovation in Clinical Trials (U44 Clinical Trial Optional)

Related Notices
  • November 30, 2023 - Notice of Change: Extension of PAR-21-224 "NeuroNEXT Small Business Innovation in Clinical Trials (U44 Clinical Trial Optional)". See Notice NOT-NS-24-037
  • November 14, 2023 - Clarification of Implementation of the NIH SBIR and STTR Foreign Disclosure Pre-award and Post-Award Requirements. See Notice NOT-OD-24-029
  • June 12, 2023 - Implementation of the NIH SBIR and STTR Foreign Disclosure Pre-award and Post-Award Requirements. See NOT-OD-23-139. (See updates incorporated into NOFO content in Sections IV, V, VI, and VIII applicable for applications submitted for due dates on or after September 5, 2023.)
  • February 23, 2023 - Notice of Change to Minimum Performance Standards for SBIR and STTR Applicants. See Notice NOT-OD-23-092.
  • NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
  • NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
  • October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available. See Notice NOT-OD-22-018.
  • September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice NOT-OD-21-181.
  • August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022. See Notice NOT-OD-21-169.
  • August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170
  • April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109
Funding Opportunity Announcement (FOA) Number
PAR-21-224
Companion Funding Opportunity

PAR-21-223 - NeuroNEXT Clinical Trials (U01 Clinical Trial Optional)

Assistance Listing Number

93.853

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) encourages small business applications for exploratory clinical trials of investigational agents (drugs, biologics, surgical therapies or devices) that may contribute to the justification for and provide the data required for designing clinical studies. Diseases chosen for study should be based on the NINDS strategic plan and clinical research interests (www.ninds.nih.gov/funding/areas/index.htm).

Successful applicants will be given access to the NeuroNEXT infrastructure. Following peer review, NINDS will prioritize and order trials that are given access to the NeuroNEXT infrastructure. The NeuroNEXT Clinical Coordinating Center (CCC) will work with the successful applicant to efficiently implement the proposed study. The NeuroNEXT Data Coordinating Center (DCC) will provide statistical and data management support. The NeuroNEXT clinical sites will provide recruitment/retention support as well as on-site implementation of the clinical protocol.

Applicants do not need to be part of the existing NeuroNEXT infrastructure.

Key Dates

Posted Date
May 05, 2021
Open Date (Earliest Submission Date)
August 05, 2021
Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

Standard dates apply

*** Note new SBIR/STTR Standard Due Dates.

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
Advisory Council Review
Earliest Start Date
Expiration Date
New Date September 06, 2024 (Original Date: April 06, 2024) per issuance of NOT-NS-24-037
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

Purpose:

To facilitate the cooperation and partnering of public and private funding organizations, universities, academic medical centers, research institutes, contract research organizations, biotechnology companies, and pharmaceutical companies, NINDS has formed the Neurology Network of Excellence in Clinical Trials (NeuroNEXT, www.NeuroNEXT.org). NeuroNEXT has a Clinical Coordinating Center (CCC), a Data Coordinating Center (DCC) and a group of 25 geographically distributed clinical sites. This clinical research network develops and conducts multiple, scientifically sound, possibly biomarker-informed exploratory clinical trials evaluating the most promising therapies, whether from academic, foundation or industry discoveries. Examples include Phase 2 clinical trials and clinical research studies aimed at validating biomarkers and clinical outcomes in preparation for clinical trials. A separate clinical trials network has been established and funded by NINDS to conduct clinical trials and biomarker studies for stroke treatment, prevention and recovery; thus NeuroNEXT has been established for the conduct of studies in neurological disorders other than stroke.

NeuroNEXT provides a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of protocols in neurological disorders affecting adult and/or pediatric populations. While the network is not specific to one disease, it has the capacity to coordinate a cadre of specialist investigators to implement studies efficiently in response to disease-specific opportunities.

The network is designed to increase the efficiency of clinical trials, to facilitate patient recruitment and retention, to increase the quality of neuroscience clinical trials, and to enable public-private partnerships.

This FOA uses the U44 cooperative agreement mechanism and is open to eligible applicants, as defined in Section III. Academic researchers may wish to consider applying through PAR-21-223"NeuroNEXT Clinical Trials (U01)". "NeuroNEXT Infrastructure Resource Access (X01)" or any reissue if they wish to gain access to the network infrastructure but do not require funds for trial costs.

Since conducting the clinical trials needed for commercialization may be capital-intensive, this FOA encourages business relationships between NIH's SBIR/STTR awardees and third-party investors and/or strategic partners. In particular, this FOA will give competitive preferences and funding priority to applications deemed likely to result in a commercial product as indicated by an applicant's ability to secure independent third-party funds.

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

Definitions:

For this funding opportunity announcement, Phase I and II clinical studies or trials refer to the common phases of a clinical trial. SBIR Phase I and II refer to the project phases of the SBIR program.

Scope of the Program:

This FOA encourages Fast Track, Phase II, and Phase IIB SBIR applications for exploratory clinical trials of investigational agents (drugs, biologics, surgical therapies or devices) that may contribute to the justification for and provide the data required for designing a future trial, for biomarker validation studies, or for proof of mechanism clinical studies. Applications for drugs or biologics should be supported by compelling scientific evidence that the investigational agent proposed for study will reach/act upon the designated target or that its mechanism of action is such that it is expected to be of benefit in ameliorating a specific aspect of the disease. Neurologic diseases chosen for study must fall within the primary responsibility of NINDS (www.ninds.nih.gov/funding/areas/index.htm). Multi-site studies in stroke prevention, treatment and/or recovery are not appropriate for this FOA; those studies would be considered by NIH StrokeNet: http://www.nihstrokenet.org/. Separate clinical trial networks also exist for the conduct of studies in neurological emergencies (SIREN: https://siren.network/) and pain (EPPIC-NET: https://www.ninds.nih.gov/Current-Research/Trans-Agency-Activities/NINDS-Role-HEAL-Initiative/NINDS-Role-HEAL-Initiative-EPPIC). Studies on these topics should be directed to the dedicated networks. Studies primarily focused on biomarker validation may also apply to one of the NINDS Biomarker funding opportunities https://www.ninds.nih.gov/Current-Research/Focus-Tools-Topics/Biomarkers.

Phase 1 clinical trials should be directed to the exploratory clinical trial FOA (PAR-18-420 and PAR-18-617). Phase 1b/2a trials requiring multi-center implementation can be considered under this FOA.

Applications in rare diseases are encouraged while recognizing that available patient pools may not be adequate to meet the sample size requirements normally required to establish the efficacy of an intervention. NINDS acknowledges that innovative, non-traditional trial designs including adaptive designs may be appropriate in rare disease studies. While NeuroNEXT is primarily intended for exploratory trials, the network will consider Phase II/III trials in diseases with a US prevalence of under 5,000 persons.

Examples of appropriate studies under this FOA include, but are not limited to, those designed to:

  • Evaluate and optimize the dose, formulation, safety, tolerability or pharmacokinetics of an intervention in the target population.
  • Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity, pharmacodynamic response, target engagement, dose-response trends) in a human "proof of concept" trial.
  • Select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., futility trials).
  • Evaluate biological activity relative to clinical endpoints.

Applications seeking to obtain data needed for pharmacometric modeling are encouraged, with the ultimate aim of enabling the optimal design of a future efficacy trial of an intervention.

For medical devices, in addition to providing initial clinical safety data, appropriate studies are those that inform the next phase of development, usually by finalizing the device design, establishing operator technique, and/or finalizing the choice of study endpoints for the design of a pivotal clinical trial.

Fast Track Studies should implement clear go-no go criteria for continuing to the next Phase II SBIR. When possible, all studies should also include go-no go criteria for proceeding to the next trial phase after the Phase II award. These should be biomarker-informed wherever possible. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-process-drug-development-tools-guidance-industry-and-fda-staff

This FOA is not intended to support the conduct of a clinical trial where the primary aim is to confirm efficacy of a proposed intervention.

Implementation:

Applicants should make note of the following:

(1) Applicants to this FOA will be required to incorporate the NeuroNEXT infrastructure (www.neuronext.org) into their proposed study. Additional (ad-hoc) sites may be proposed to fulfill specific study requirements. All applicants will be required to use the master clinical trial agreements and central IRB that have been established for NeuroNEXT.

(2) Rationale: Exploratory trials primarily test hypotheses in relatively small programs so that the acceptable risk and uncertainty are higher than in later stage programs. Exploratory clinical trials must anchor their rationale in (1) an unmet medical need; (2) a plausible biological mechanism; (3) non-clinical (in vitro and/or in vivo) data; and/or (4) early clinical data. Their individual weight should be carefully assessed in the specific context of the application at hand.; there is no requirement to provide support from all four areas. However, supporting data should be robust enough to justify the proposed phase of study. Applicants should consider the limitations of those studies with regards to the scientific rigor guidelines published by NINDS (see https://grants.nih.gov/grants/guide/notice-files/NOT-NS-11-023.html). Preclinical data (such as from animal studies) that do not sufficiently meet the rigor guidelines or are not sufficiently associated with the human condition may be inadequate to support the rationale for the study.

(3) Secondary Aims:

Issues of study feasibility and refinement of study procedures may be addressed as secondary aims in an exploratory clinical trial, but not as the primary aim. Examples of such secondary aims include, but are not limited to, the following:

  • Determining the optimal measure (endpoint), its variability, and/or the optimal timing of outcome evaluations in the context of the intervention,
  • Collecting information on the utility of questionnaires, rating scales, or biomarkers,
  • For Early Feasibility or Traditional Feasibility studies of medical devices, issues of study feasibility and refinement of study procedures are expected to be addressed as primary aims in addition to providing initial clinical safety data at this stage. These may include:
  • Identifying appropriate modifications to the procedure or device to enable a subsequent Pivotal study on a finalized system;
  • Refining the intended use population;
  • Developing and refining data collection procedures;
  • Refining the non-clinical test plans or methodologies; and
  • Developing subsequent clinical study protocols.

(4) The NIH recognizes that devices can vary greatly in terms of basic form and function, physiological bases for therapy, degree of invasiveness, etc. Consequently, the appropriate pathway to market may require a traditional Feasibility and Pivotal study in support of an eventual Pre-Market Approval submission, or may require a more limited study to address specific issues in support of an FDA 510(k) or 510(k) De Novo submission. Clinical studies involving devices may utilize the entire NeuroNEXT Network, or a more limited subset of centers selected based on appropriate expertise for the given device. Investigators are encouraged to contact NINDS Scientific/Research Staff as early as possible to discuss how the NeuroNEXT network may best be utilized in support of their specific device project.

NINDS anticipates that the majority of device projects utilizing NeuroNEXT will be traditional Feasibility Studies in order to best leverage the advantages of the network. A Traditional Feasibility Study is a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan a Pivotal Study. If an Early Feasibility Study is proposed, it should be designed in accordance with FDA's draft guidance, "Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies", to allow for early clinical evaluation of devices to provide proof of principle and initial clinical safety data while device design and operations are still in development. Early Feasibility and Traditional Feasibility study designs may include single-arm case series, on-off interventions (patients as own controls), device-device comparisons, comparisons to historic controls, comparisons to performance controls, or adaptive/Bayesian designs.

(5) Rare Diseases: Applications in rare diseases are encouraged while recognizing that available patient pools may not be adequate to meet the sample size requirements normally required to establish the efficacy of an intervention. NINDS acknowledges that innovative, non-traditional trial designs including adaptive designs may be appropriate in rare disease studies. Regardless of the design it is especially important to ensure that the study design and statistical analysis plans will meet the stated objectives,and allow for the most efficient evaluation of the limited subjects. The application should clearly demonstrate recruitment feasibility at the participating sites and applicants are encouraged to fully engage patient advocacy groups or similar representatives of the affected disease community in study design, execution, and reporting. While NeuroNEXT is primarily intended for exploratory trials, the network will consider Phase 2/3 trials in diseases with a US prevalence of under 5,000 persons.

(6) The award and continuation of funding are subject to milestones to be specified in the notice of grant award according to NINDS policies.

(7) NIH Resources: As appropriate, applicants are encouraged to make use of the following resources for clinical research including:

(a) Clinical and Translational Science Award (CTSA) program (https://ncats.nih.gov/ctsa);

(b) NeuroQOL (http://www.neuroqol.org);

(c) NIH Toolbox (http://www.nihtoolbox.org);

(d) PROMIS (http://www.nihpromis.org); and

(e) NINDS Common Data Elements (http://www.commondataelements.ninds.nih.gov).

(8) Mobile Technologies: Applicants are encouraged to consider utilizing (at least experimentally) mobile technologies to facilitate data collection and protocol adherence on the part of research participants and study site staff.

(9) For Biomarker Validation Studies, biomarkers are defined as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Categories of biomarkers include: Susceptibility/risk, diagnostic, monitoring, prognostic, predictive, pharmacodynamic/response, and safety. Biomarker studies should define their intended Context of Use (a statement that fully and clearly describes the way the biomarker will be used in future clinical trials).

Working with NeuroNEXT is a cooperative venture between NINDS, the NeuroNEXT network and the applicant. NINDS will provide guidance to potential applicants with input from NINDS Program Staff and the NeuroNEXT Executive Committee. Potential applicants are strongly encouraged to contact NINDS Scientific/Research Contacts (see Agency Contacts, Section VII) in order to discuss the feasibility of conducting the proposed trial through the NeuroNEXT infrastructure before submitting an application. Pre-application consultation may include an introductory teleconference (at least 3 months prior to submission), followed by a conference call or in-person meeting with NINDS staff, as needed.

Funding decisions will also be based on a study's fit for the network relative to other proposed and ongoing trials.

Prior to grant award, awardees who do not have an exemption from the FDA must provide any additional FDA correspondence regarding the status of the protocol to the NINDS, especially if the trial has been placed under full or partial hold.

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

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New (Fast-Track)
New (SBIR Direct Phase II)
Renewal (Phase II)
Resubmission (all phases)
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for 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.

Award Budget

Applicants should rarely exceed $1,000,000 in total cost per year for a Phase I and $1,500,000 in total cost per year for a Phase II/Phase IIB. Applicants are strongly encouraged to contact NIH program officials prior to submitting any application in excess of the guidelines and early in the application planning process. In all cases, applicants should propose a budget that is reasonable and appropriate for completion of the research project.

Award Project Period

Durations up to 2 years for a Phase I and up to 3 years for Phase II may be requested.

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;
    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.
  3. 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.

Performance Benchmark Requirements

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 and the SBIR and STTR Extension Act of 2022. The benchmark establishes a minimum number of Phase II awards the company must have received relative to a given number of Phase I awards received during the 5-fiscal year time period. 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 Transition Rate requirement, agreed upon and established by all 11 SBIR agencies, was published for public comment in a Federal Register Notice on October 16, 2012 (77 FR 63410) and amended on May 23, 2013 (78 FR 30951).

  • For 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): Companies that do not meet or exceed the benchmark minimum Transition Rate of 0.25 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. This requirement does not apply to companies that have received 20 or fewer Phase I awards over the prior 5-fiscal year period.
  • For application deadlines that fall on or after April 5, 2023: For SBIR and STTR Phase I applicants that have received more than 50 Phase I awards over the past 5 fiscal years (excluding the most recently-completed fiscal year): Companies that do not meet or exceed the benchmark minimum Transition Rate of 0.5 will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 50 or fewer Phase I awards over the 5-fiscal year period.

On June 1 of each year, SBA will identify the companies that fail to meet minimum performance requirements.SBA calculates individual company Phase I to Phase II Transition Rates using SBIR and STTR award information across all federal agencies. SBA will notify companies and the relevant officials at the participating agencies. More information on the Phase I to Phase II Transition Rate requirement is available at SBIR.gov.

Phase II to Commercialization Benchmark: In accordance with guidance from the SBA, the HHS 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 and the SBIR and STTR Extension Act of 2022. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537), with a reopening of the comment period published on September 26, 2013 (78 FR 59410).

  • For companies that have received more than 15 Phase II awards from all agencies over the past 10 fiscal years (excluding the two most recently completed fiscal year): 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 during the past 10- fiscal year period. Applicants that fail this benchmark 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. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently-completed fiscal years.
  • For application deadlines that fall on or after April 5, 2023: For companies that have received more than 50 Phase II awards from all agencies over the past 10-fiscal years (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $250,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period. Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 50 or fewer Phase II awards over the 10-fiscalyear period, excluding the two most recently-completed fiscal years.
  • For application deadlines that fall on or after April 5, 2023: For companies that have received more than 100 Phase II awards from all agencies over the past 10-fiscal years (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $450,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period. Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 100 or fewer Phase II awards over the 10-fiscalyear period, excluding the two most recently-completed fiscal years.

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.

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.

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.

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

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

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

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:

Facilities & Other Resources (Applicable to applications submitted for due dates on or after September 5, 2023)

In addition to describing the scientific environment and the company support, the applicant must describe the business environment and resources, or how the company will obtain access to the appropriate business resources, for completing and commercializing the proposed product or service. This includes any relevant intellectual property associated with the project necessary to facilitate commercialization.

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.

Where applicable, the following optional elements may also be provided in the appendix:

Non-referenced or non-published, non-standardized clinical assessments and data collection tools.

Investigator Brochures, see 21 CFR 312.23 (a)(5) for format

Clinical pharmacology justifying the proposed dosing regimen

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.

The budget should be largely planned on a fee-for-service basis with detailed per-patient costs. That budget may include clinical trial costs such as:

  • Up to 4 person months for the protocol PD(s)/PI(s) (even if that person is also a NeuroNEXT site PD(s)/PI(s)
  • Up to 3 person months support for a study-specific clinical coordinator at the applicant's site if the NIH-funded site coordinator is at capacity with NeuroNEXT trials or does not have necessary expertise to assist with the proposed study. If the applicant is not at a NeuroNEXT clinical site, up to 12 person months support for a study-specific clinical coordinator may be included.
  • Study-related procedures/materials
  • Clinical site operations for any ad hoc sites which are proposed

The budget will not include costs which are already covered by the NINDS infrastructure:

  • NeuroNEXT site PD(s)/PI(s) time other than the protocol PD(s)/PI(s)
  • NeuroNEXT site coordinator time
PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) applicants are required to address a Data Management and Sharing Plan, regardless of the amount of direct costs requested for any one year. However, SBIR and STTR recipients may retain the rights to data generated during the performance of an SBIR or STTR award for up to 20 years after the award date, per the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Program Policy Directive. An acceptable Data Management and Sharing plan can reference and incorporate these data rights. Further information about SBIR and STTR data rights are enumerated in the NIH GPS.

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

Specific Aims:

Applicants should describe the potential impact of the proposed research. The hypotheses and specific aims of the trial must be clearly and concisely stated. Data or evidence of the capability, completeness of design, and efficacy must be provided in the application, along with the rationale for selection of the criteria used to validate the technology, prototype, or method, similar to a Phase I final report required in standard Phase II applications.

Research Strategy:

Significance and Biological Relevance: Applicants are encouraged to state concisely the need, rationale, and scientific relevance of the proposed research. It is particularly important that there be a discussion of how the trial will test the hypothesis proposed and how results of the trial (positive or negative) may be explained based on the biological action of the proposed intervention. The application must present an overview of the state of the science, current status of therapeutics for the disease, and relevance of the trial for treatment of the disease. The applicant should also identify other (industry or academic) current or planned trials that potentially overlap with the proposed study. The timeliness of the proposed study should be discussed in the application.

Potential Impact of the trial:Applicants should also include a description of the potential impact of the proposed research on clinical care - regardless of the results - and estimate the public health impact relative to the number of afflicted individuals in the U.S. and/or global population annually.

Prior Studies and Rationale for Development: Exploratory trials primarily test hypotheses in relatively small programs so that the acceptable risk and uncertainty are higher than in later stage programs. Exploratory clinical trials to address an unmet medical need or to improve current standards of care must anchor their rationale in (1) a plausible biological mechanism; (2) non-clinical (in vitro and/or in vivo) data; and/or (3) early clinical data. The individual weight should be carefully assessed in the specific context of the application at hand; there is no requirement to provide support from all three areas. While the NINDS recognizes that informative animal models are not available for many neurological disorders, the applicant should specifically address the rigor of any animal studies being used as support. If the animal model and efficacy read-out are not sufficiently associated with the human condition, and/or if pre-clinical data (such as for example animal studies) do not sufficiently meet the NINDS rigor guidelines, then applicants should consider not using them as primary support of the study rationale. Applicants should describe the full body of evidence being used to support the proposed study and comment on the justification for moving forward with the proposed clinical study. The major findings of the studies, whether pre-clinical or clinical, that led to the proposed clinical trial should provide a compelling rationale for the belief that the proposed intervention warrants study.

Approach: Applicants should provide a brief description of their proposed study, including the following:

  • A description and rationale for the selected trial design.
  • A description of the study population and why it is an appropriate group to answer the question under study.
  • A description and rationale for selection of the study outcomes and endpoints.
  • A description of the intervention to be tested and how it will be administered.
  • A description of all assessments including clinical, laboratory, physiological, behavioral, patient-centered, or other outcomes addressing the primary and secondary research questions. Use of patient reported outcomes, including those available through PROMIS and NeuroQoL, as well as non-traditional data collection approaches (e.g., telephone, mobile devices or web-based systems) should be considered.
  • A discussion regarding how the following resources for clinical research will be utilized, as applicable:
  • NeuroQOL (http://neuroqol.org);
  • NIH Toolbox (http://www.nihtoolbox.org);
  • PROMIS (http://nihpromis.org); and
  • NINDS Common Data Elements (http://www.commondataelements.ninds.nih.gov)
  • A discussion of potential biases and/or challenges in the protocol and how they will be addressed.
  • A discussion of how the study investigators will be kept blinded to treatment group-specific data during the course of the clinical trial
  • Clear go-no/go decision criteria for proceeding to phase III trials should be specified.

All clinical procedures should be in compliance with good clinical practice (GCP) standards where applicable.

A study protocol synopsis should be included. Following peer review, applicants who are granted network access will work with the NeuroNEXT team and the NINDS and additional minor refinements and operational changes can be made if needed. The NeuroNEXT infrastructure has been established by NINDS based on peer- and Council review to form a group of outstanding clinical trial experts from the field of neurology and statistics with a proven record of developing high quality protocols.

Letters of Support:

Include letters of support documenting any commitments from third-party investors. Letters of support from these institutional partners should indicate any actual or planned/conditional financial commitment as a specific dollar figure or range, consistent with the instructions provided under Section IV.2, Other Attachments, "Fundraising Plan". Appropriate documentation of third-party investor commitment(s) may include a conditional letter of support stating that the third-party funding is contingent upon NIH selecting the application for an award.

SBIR-eligible public companies may include as part of their fundraising plan the issuance of stock. In such a case, the preferred documentation is a letter of support, signed by the Chairman of the Board of Directors, which stipulates the following: (1) the amount of capital raised from the issuance of stock; (2) the amount of capital that will be dedicated to the proposed project under this FOA; (3) sufficient information regarding the use of the dedicated capital to demonstrate a substantial, value-added contribution toward the development and commercialization of the product or service to be developed under this FOA.

All letters should be combined into a single PDF and uploaded as the Letters of Support attachment.

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:

It is expected that the network-developed research resources such as Manual of Operations, study manuals, case-report forms, phenotype ascertainment instruments, and newly developed common data elements will be made available to the public 18 months after publication of study findings, consistent with achieving the goals of the program.

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.

SBIR/STTR Information

All instructions in the SF 424 (R&R) SBIR/STTR Application Guide must be followed, with the following additional instructions:

Commercialization Plan: All applicants are expected to describe a realistic plan (extending beyond SBIR Phase II or Phase IIB), which outlines how and when full commercialization can be accomplished.

The following subsections with the headings should be included within the Commercialization Plan, in addition to the requirements listed in the SF424 Application Guide.

1) Statement of Need

Applicants must provide a concise "Statement of Need". This statement is expected to provide answers to the questions listed below:

  • What is the perceived "Valley of Death" for the product/technology under development?
  • Why is additional government funding critically needed to accelerate the development of the product or technology toward commercialization? Specifically, what activities are being proposed under this FOA that would not otherwise be possible through independent third-party investments OR would be significantly delayed without additional NIH support?
  • To what extent would a possible award under this FOA advance the product or technology far enough to attract sufficient, independent third-party financing and/or strategic partnerships to carry out full commercialization?

2) SBIR/STTR Commercialization History

Applicants should provide an SBIR/STTR Commercialization History that addresses the questions listed below. The following questions should be addressed for all SBIR/STTR awards received from ANY Federal agency:

  • Has the company gone through any name changes within the past five years? If so, then all previous company names should be listed in the application.
  • Is the company a subsidiary or a spin-off? If so, then the name of the parent company should be provided.
  • What percentage of the company's revenue was derived from SBIR/STTR funding during each of the past 5 years, including both Phase I and Phase II awards? Applicants should report a percentage value for each year individually.
  • What is the total number of SBIR/STTR Phase II awards that the company has received from the Federal government? For each award, companies should provide the award number, the award amount, project duration, and the name of the awarding agency.
  • What are the total revenues that have been generated to date as a result of the commercialization of the SBIR/STTR projects funded within the past 5 years?

3) Fundraising Plan

Applicants are expected to provide a Fundraising Plan. This plan is expected to include the following information:

  • A detailed and specific plan for securing substantial, independent third-party investor funds either at the time of award or after the completion of the Phase II/Phase IIB.
  • The type(s) of independent third-party investor funds (i.e., cash, convertible debt, etc.) that will be secured during the project period or after the completion of the trial.
  • The source(s) of independent third-party investor funds (e.g., venture capital, state funds) that will be secured during the project period or after the completion of the trial.

If independent third-party investor funds will be secured during the project period please include:

1) The total amount of independent third-party investor funds that will be secured during the project period.

2) The anticipated schedule for receiving independent third-party investor funds, including any relevant terms and conditions if available.

3) Sufficient information regarding the use of any their-party support

The NINDS considers the raising of independent third-party investor funds to be an important means to facilitate and accelerate the capital-intensive steps that are required to commercialize new products/technologies emerging from NIH-funded SBIR/STTR Phase II projects.

Examples of third-party investors include, but are not necessarily limited to, another company, a venture capital firm, an individual "angel" investor, a foundation, a university, a research institution, a State or local government, or any combination of the above. SBIR-eligible public companies may also include as part of their fundraising plan the issuance of stock.

Applicants are expected to document their matching funds (or plans for raising them) as concretely as possible. For example, plans to raise additional funds from venture capital companies and/or other pharmaceutical companies should name specific partners and investors. Documentation should be included in the Appendix materials.

It is likely that several months will have elapsed between the time an application is submitted and the time it is peer reviewed and subsequently considered for possible funding. Accordingly, applicants should present a detailed summary of all past and/or planned (i.e., future/expected) third-party investor funds which clearly shows, relative to the estimated award date, when these funds have been and/or will be secured. For example, if the fundraising efforts of the SBC are in progress, and/or if the third-party investment is contingent upon NIH selecting the application for funding, then such plans should be clearly described in the Fundraising Plan.

4) Company

Follow the instructions provided in the SF424 Application Guide, with the following additions: An objective of the SBIR and STTR programs is to foster and encourage participation in innovation and entrepreneurship by socially and economically disadvantaged persons and women-owned small businesses. Describe the company’s approach to attract and retain new and senior employees with diverse backgrounds underrepresented in the- in the entrepreneurial, biomedical, behavioral, or clinical research workforce (see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-20-031.html). Such individuals may include those from underrepresented racial and ethnic groups, those with disabilities, women, and those from disadvantaged backgrounds (https://www.sba.gov/contracting/government-contracting-programs/8a-business-development-program/eligibility-requirements/social-disadvantage-eligibility)?.

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.

With the following additional instructions:

Section 2 - Study Population Characteristics

2.7 Study Timeline

Milestones:

Applications must include proposed yearly go/no-go milestones. While final milestones will be determined at the time of award, the applicant should propose clear milestones that provide objective, quantitative outcomes that will justify continuing the project. Milestones are not equivalent to aims but rather are determinants of whether a study continues or stops. The applicant should endeavor to present a) the goals and timeline for completion while setting milestones at the end of each funding year, (b) the criteria for success defined as justification for continuation of the project, and (c) the rationale for the choice of parameters tested and quantitative values as decision points, where possible.

  • The proposed milestones must include achievable goals for the start-up stage, feasibility stage, and completion stage of the project as follows:
  • Completion of start-up activities (finalization of protocol, contracting of sites, registration in ClinicalTrials.gov, completion of any final regulatory approvals, etc.)
  • Enrollment of the first subject
  • Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study subjects, including women, minorities and children (as appropriate)
  • Expected timing of proposed interim analyses and, for adaptive designs, implementation of pre-specified adaptation plan
  • Completion of data collection time period
  • Completion of primary endpoint and secondary endpoint data analyses
  • Completion of final study report
  • Publication of primary study results
  • Reporting of results in ClinicalTrials.gov
  • Submission of final public use dataset to NINDS
Delayed Onset Study

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

PHS Assignment Request Form

All instructions in the SF424 (R&R) 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, NIH. Applications that are incomplete or non-compliant will be withdrawn.

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

Section V. Application Review Information

1. Criteria

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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.

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 proposed clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation

For this particular announcement, note the following:

1. Approved projects will be implemented through the NeuroNEXT infrastructure and will make use of previously approved sites, resources, and investigators at the NeuroNEXT Clinical Coordinating Center, Data Coordinating Center, and clinical sites. The applicant will work closely with the NeuroNEXT investigators who have been selected for their experience and training in neurological clinical research. While some applicants will be relatively junior in their careers, NeuroNEXT provides a cadre of experienced clinical trial experts who can ensure high quality implementation and oversight of studies. The PD(s)/PI(s) therefore do not need to bring as much clinical research experience as they would have to bring to a non-NeuroNEXT project.

The NeuroNEXT infrastructure (CCC, DCC and clinical hubs) was selected following peer review to provide an optimal environment and mechanism for conducting relevant projects, including centralized clinical trial management, data management, and oversight of activities at clinical centers.

2. Exploratory clinical trials must anchor their rationale in (1) an unmet medical need; (2) a plausible biological mechanism; (3) non-clinical (in vitro and/or in vivo) data; and/or (4) early clinical data. Their individual weight should be carefully assessed in the specific context of the application at hand; the applicant is not required to provide support from all four areas. Reviewers will focus on the overall impact of the study which will also include the evaluation of the experimental design and all of the review criteria described below

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?)

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?

How compelling is the justification for the development of the proposed intervention in terms of potential advances in clinical practice, public health, and/or patient quality of life? How convincing is the evidence that equipoise exists in the medical and patient communities and the intervention is ready for clinical development?

Is it clear why the proposed exploratory trial is essential to inform the design and implementation of a subsequent efficacy trial, or enable a go/no-go decision regarding further clinical development of the intervention? Is it clear how the proposed intervention would impact the disease and the patients?

Does the proposed trial have the potential to advance the field (e.g., by evaluating a new target mechanism, or by advancing the validation of a biological or clinical outcome) even if (a) the proposed study design, methods, and intervention are not innovative, and/or (b) the results of the trial indicate that further clinical development of the intervention is unwarranted?

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?

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? Evaluate whether the PDs)/PI(s) of the project is/are well-positioned to provide scientific leadership to the proposed study while collaborating with the NIH NeuroNEXT CCC, DCC and site investigators. Is there evidence of adequate commitment and scientific input from the NIH NeuroNEXT leadership?

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?

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?

How adequate are the study documents (e.g., protocol, consent, investigator's brochure) to allowing the implementation of a high quality study? Do the study documents comply with Good Clinical Practice (GCP)?

How well does the project leverage the use of existing NIH tools, NINDS networks, and/or other resources?

While the NIH NeuroNEXT environment has already undergone peer review and is fully established, the following issues should be considered with respect to each application: Have the sites provided adequate or reasonable estimates of the number of patients that they expect to be able to enroll? Does this project include a partnership with the private sector (e.g. patient groups and/or industry), and if so, have agreements with proposed partners been established? Have any foreign organizations involved in the proposed study documented the compatibility of their data collection methods with U.S. data collection methods? Is there evidence that the study drug or device will be available in sufficient quantities to ensure feasibility of the project? Are substantive letters of support or other documentation provided to assure commitment of subcontractors, consultants, and/or service agreements for personnel and facilities?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

How appropriate are the primary and secondary outcome measures? How appropriate are the eligibility criteria, randomization plan (if applicable), methods of blinding, sample size, trial power, data management plans, and plans for training of site personnel?

How appropriate are the plans for subject outreach, recruitment, retention and follow-up?

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?

Are there characteristics of the proposed research that specifically lend themselves to deployment within the NeuroNEXT infrastructure?

In addition, for applications involving clinical trials

If proposed, are the plans to use 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?

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?

To what extent does the applicant SBC have the ability to address regulatory issues, either through their own staff members or through appropriate arrangements with external regulatory consultants?

Additional Review Criteria

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

Study Timeline

Specific to applications proposing clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

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

How appropriate are the CT milestones? How likely is the trial to be completed within the project period?

Commercialization Criteria

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:

  • To what extent do the prior experience and qualifications of the project team members, as well as their applicant's business alliances and/or corporate partnerships, 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?
  • 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?
  • Is an appropriate approach to enhancing diversity and inclusion in the company discussed?

Intellectual Property (IP):

How strong is the applicant's intellectual property (IP) portfolio/position (pertinent to the proposed Project), and to what extent does the company have a reasonable strategy to protect its IP going forward?

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

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 Scientific Review Branch, NINDS in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

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

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

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
  • Security risk as assessed by the HHS Due Diligence Program (for due dates on or after September 5, 2023).

Disclosure Requirements Regarding Ties to Foreign Countries (Applicable for applications submitted for due dates on or after September 5, 2023)

Upon request applicants are required to disclose all funded and unfunded relationships with foreign countries, using the Required Disclosures of Foreign Affiliations or Relationships to Foreign Countries form (referred to as the "Disclosure Form" hereafter), for all owners and covered individuals. A "covered individual" is defined as all senior key personnel identified by the SBC in the application (i.e., individuals who contribute to the scientific development or execution of a project in a substantive, measurable way).

Upon request, applicants must submit the completed Disclosure Form and any additional agency-specific information electronically in eRA Commons via the Just-In-Time (JIT) process as described in the NIH Grants Policy Statement (GPS) Section 2.5.1 Just-in-Time Procedures. Applicants must continue to comply with NIH Other Support disclosure requirements as provided in NIH GPS Section 2.5.1 and may be required to provide similar information on the Disclosure Form for covered individuals identified in the application. If participating in this NOFO, SBC applicants applying to CDC and FDA will follow each agency's policies for submitting additional documents during the pre-award process. Applicants that do not submit the completed Disclosure Form during the JIT process will be deemed noncompliant and not be considered for funding.

Denial of Awards (Applicable for applications submitted for due dates on or after September 5, 2023)

Applicants are encouraged to consider whether their entity's relationships with foreign countries of concern will pose a security risk. Prior to issuing an award, NIH (and CDC or FDA, as applicable) will determine whether the SBC submitting the application:

  • has an owner or covered individual that is party to a malign foreign talent recruitment program;
  • has a business entity, parent company, or subsidiary located in the People's Republic of China or another foreign country of concern; or
  • has an owner or covered individual that has a foreign affiliation with a research institution located in the People's Republic of China or another foreign country of concern.

A finding of foreign involvement with countries of concern will not necessarily disqualify an applicant. Final award determinations will be based on the above finding of foreign involvement and whether the applicant's involvement falls within any of the following risk criteria, per the Act:

  • interfere with the capacity for activities supported by NIH, CDC, or FDA to be carried out;
  • create duplication with activities supported by NIH, CDC, or FDA;
  • present concerns about conflicts of interest;
  • were not appropriately disclosed to NIH, CDC, or FDA;
  • violate Federal law or terms and conditions of NIH, CDC, or FDA; or
  • pose a risk to national security.

Generally, NIH, CDC, and FDA will not provide SBC applicants the opportunity to address any identified security risks prior to award. NIH, CDC, and FDA will not issue an award under the SBIR/STTR program if the covered relationship with a foreign country of concern identified in this guidance is determined to fall under any of the criteria provided .

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

For applications submitted for due dates on or after September 5, 2023, SBIR and STTR applicants under consideration for award will be required to submit the SBA U.S. Small Business Administration (SBA) issued the Required Disclosures of Foreign Affiliations or Relationships to Foreign Countries form during the JIT process. Applicants that fail to submit a Disclosure Form will not be considered for funding.

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.

All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

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

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

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 OMB administrative guidelines, HHS 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 recipientsis 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 recipientsfor the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

Defining of research objectives and approaches,

Planning, conducting, analyzing, and publishing results, interpretations, and conclusion of their studies and for providing overall scientific and administrative leadership for the Research Project.

Supervising of the clinical study with consistent emphasis on collaborative interactions between investigators, advisory and steering committees, and NINDS representatives.

Interacting with the NeuroNEXT Clinical Coordinating Center and the NeuroNEXT Data Coordinating Center as well as any ad hoc sites.

Acquiring an IND from the FDA if an investigational agent is to be used,

Acting as a member of the NeuroNEXT steering committee for the duration of the study with possible participation in steering groups for planning, quality control, capitation, publications etc.

Recipientswill retain custody of and have primary rights to data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

NINDS staff involvement will include oversight of the IRB approved protocol by the NINDS Program Official, documentation of adequate serious adverse event management and reporting, and regular communications with the principal investigator and staff; additional involvement generally includes participation in meetings of the steering committee and other leadership committees. Specifically:

An NINDS Project Scientist working with the network investigators will develop milestones for the study. Failure to meet the agreed upon milestones may result in reduced funding or early termination of the cooperative agreement. The NINDS retains the option to obtain periodic external peer review of progress.

The NINDS Project Scientist will function as one of several co-investigators, collaborating and interacting as necessary with the Principal Investigators in accomplishing the overall goals of the Research Program.

In addition, an NINDS Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

A separate NINDS Program Official, from the Office of Clinical Research, will serve as the NINDS liaison to the Data and Safety Monitoring Board,if it is determined a DSMB is needed for the study.

If the proposed trial should require that FDA issue an IND, the NINDS Project Scientist and/or Program Official(s) will be present at any meetings held with the FDA related to this NIH-funded protocol.

As with any award, even during the period recommended for support, continuation is conditional upon satisfactory progress. If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NINDS will consider ending support and negotiating a phase-out of the award. The NINDS retains the option to obtain periodic external peer review of progress. Milestones will be established by the NINDS prior to the award of the grant based on recommendations from the primary review group. NINDs will make an award for 2 to 3 years in order to start-up the trial and establish performance feasibility. Continuation of the award past this feasibility period will be contingent upon a demonstrated ability to meet milestones indicating that the trial can be implemented as planned. Feasibility milestones will be defined at the start of each trial and will be monitored closely by the Institute-appointed Data and Safety Monitoring Board (DSMB) and NINDS Program Official. Achievement of these milestones will be evaluated by NINDS prior to releasing funding for each year of the award and failure to achieve these milestones may lead to study termination.

Areas of Joint Responsibility include:

None; all responsibilities are divided between recipientsand NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to dispute resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16. l

Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement (GPS). Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. SBIR and STTR recipients may retain the rights to data generated during the performance of an SBIR or STTR award for up to 20 years after the award date, per the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Program Policy Directive. An acceptable Data Management and Sharing plan can reference and incorporate these data rights. Further information about SBIR and STTR data rights are enumerated in the NIH GPS.

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.

Disclosure of Foreign Relationships Reporting Requirements (Applicable for applications submitted for due dates on or after September 5, 2023)

Recipients are responsible for monitoring their relationships with foreign countries of concern post-award, for any changes that may impact previous disclosures. SBCs receiving an award under the SBIR/STTR program are required to submit an updated Disclosure Form to report any of the following changes to NIH (and CDC or FDA, as applicable) throughout the duration of the award:

  • any change to a disclosure on the Disclosure Form;
  • any material misstatement that poses a risk to national security; and
  • any change of ownership, change to entity structure, or other substantial change in circumstances of the SBC that NIH, CDC, and FDA determine poses a risk to national security.

Regular, annual updates are required at the time of all SBIR/STTR annual, interim, and final Research Performance Progress Reports (RPPRs). For changes that occur between RPPR submissions, updated Disclosure Forms are required within 30 days of any change in ownership, entity structure, covered individual, or other substantive changes in circumstance, as described above. Recipients are required to upload these updated disclosures using the Additional Materials (AM) tool in eRA Commons.

If the recipient reports a covered foreign relationship that meets any of the risk criteria prohibiting funding described in this NOFO, NIH, CDC, and FDA may deem it necessary to terminate the award for material failure to comply with the federal statutes, regulations, or terms and conditions of the federal award. Refer to NIH GPS Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support for more information. Recipients are encouraged to monitor their covered foreign relationships post-award and avoid entering into relationships, both funded and unfunded, that may pose a security risk and jeopardize their ability to retain their award.

Agency Recovery Authority and Repayment of Funds

An SBC will be required to repay all amounts received from NIH under the award if either of the following determinations are made upon assessment of a change to their disclosure:

  • the SBC makes a material misstatement that NIH determine poses a risk to national security; or
  • there is a change in ownership, change in entity structure, or other substantial change in circumstances of the SBC that NIH determine poses a risk to national security.

The repayment requirements and procedures provided in Section 8.5.4 Recovery of Funds of the NIH GPS apply and may also be subject to additional noncompliance and enforcement actions as described in Section 8.5.2 of the GPS. Recipients are required to follow the repayment procedures provided in the Guidance for Repayment of Grant Funds to the NIH.

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: 301-637-3015

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)

Sophie Cho, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Tel: 301-529-7157
hyunjoo.cho@nih.gov

Joan Ohayon
National Institute of Neurological Disorders and Stroke (NINDS)
Tel: 301-814-2977
ohayonj@ninds.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)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.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 45 CFR Part 75 and 2 CFR Part 200.

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, P.L. 115-232, and P.L. 117-183. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.

The STTR Program is mandated by the Small Business Reauthorization Act of 1997 (P.L. 105-135), and reauthorizing legislation, P.L. 107-50, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), as reauthorized and extended under P.L. 114-328, Section 1834, P.L. 115-232, and P.L. 117-183. The basic design of the NIH STTR Program is in accordance with the Small Business Administration (SBA) STTR Policy Directive.


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