Part 1. Overview Information

Key Dates

It is critical that applicants follow the SBIR/STTR (B) Instructions in the How to Apply – Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts).

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

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

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

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

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 formed the Network for  Excellence in Neuroscience Clinical Trials (NeuroNEXT: https://neuronext.org. NeuroNEXT has a Clinical Coordinating Center (CCC), a Data Coordinating Center (DCC) and a group of 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. Applicants to this NOFO 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.

This NOFO 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 OTA-24-013 f(Stage 1 Preliminary) and OTA-24-014 Stage 2 Protocol) “NeuroNEXT Clinical Trials ”.

Since conducting the clinical trials needed for commercialization may be capital-intensive, this NOFO encourages business relationships between NIH's SBIR/STTR awardees and third-party investors and/or strategic partners. In particular, this NOFO 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.

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 NOFO encourages Phase II 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/. A separate clinical trial network also exists for the conduct of studies in neurological emergencies (SIREN: https://siren.network/). 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/focus-biomarkers-research.

Applications proposing primarily phase 1 and 3 clinical trials should be directed to the exploratory clinical trial NOFO, PAR-22-142 (https://grants.nih.gov/grants/guide/pa-files/PAR-22-142.html) and the efficacy clinical trial NOFO, PAR-21-237 (https://grants.nih.gov/grants/guide/pa-files/PAR-21-237.html) respectively, or their reissues. 

Examples of appropriate studies under this NOFO 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.
• Validate biomarkers that are fit-for-purpose for a specific context of use and can be used in future clinical trials.
• 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.
• 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.

This NOFO is not intended to support the conduct of a clinical trial where the primary aim is to confirm efficacy of a proposed intervention. While NeuroNEXT is primarily intended for exploratory trials, the network will consider Phase II/III trials in rare diseases with a US prevalence of under 200,000 persons as defined in the Rare Diseases Act of 2002 (Public Law 107-280 (https://www.gpo.gov/fdsys/pkg/PLAW-107publ280/content-detail.html)). Phase 1b/2a trials requiring multi-center implementation can be considered under this NOFO.

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) 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.

 Applicants should make note of the following:

(1) Medical devices: 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  a more limited study to address specific issues in support of an FDA 510(k) or 510(k) De Novo submission. 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. 

(2) 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). 

(3) 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 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.

 Applications Not Responsive to this NOFO

• Nonclinical studies of disease mechanism or therapeutic mechanism of action studies 
• Animal studies 
• Single site studies 
• Research focused entirely on natural history studies

Applications considered non-responsive will be withdrawn prior to review.

This NOFO requires a Community Engagement and Research Inclusion (CERI) Plan which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a CERI Plan are based on descriptions of how community engagement strategies and community-engaged research will be employed during the planning period of the proposed study; specifically, five components, a) communities of interest, b) community partners (if applicable), c) partnership development, d) strategy for incorporation of input, and e) success evaluation metrics. Applications that fail to include a CERI Plan will be considered incomplete and will be administratively withdrawn before review.

The CERI Plan will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully.

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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

1. Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United States economy through payment of taxes or use of American products, materials or labor;

2. Is in the legal form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust or cooperative, except that where the form is a joint venture, there must be less than 50 percent participation by foreign business entities in the joint venture;

3.

i. 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

ii. 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

iii. SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with § 121.705(b) concerning registration and proposal requirements.

4. Has, including its affiliates, not more than 500 employees.

 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  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  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. 

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 How to Apply – 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-fiscalyear 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-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 100 Phase II awards from all agencies over the past 10-fiscalyears (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-fiscal year period, excluding the two most recently completed fiscal years.

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply – Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • Unique Entity Identifier (UEI) – A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• SBA Company Registry – See How to Apply – Application Guide for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a UEI to complete this registration. SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019. 

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

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 How to Apply – 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 How to Apply – Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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, 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. NIH Grants Policy Statement 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review. (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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. Recipients of Phase I and Phase II grants, cooperative agreements, or contracts are eligible to submit Phase II and Phase IIB grant applications, respectively, for this opportunity in accordance with each awarding component's guidance in the current SBIR/STTR Program Descriptions and Research Topics for the NIH, CDC and FDA.

In SBIR Phase II/IIb, 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).  

Deviations from these requirements may be considered on a case by case basis. Please contact a program officer for additional information. Deviations must be approved in writing by the Grants Management Officer (GMO) 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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the SBIR/STTR (B) Instructions in the How to Apply – Application Guide, except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply – 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

All page limitations described in the How to Apply – Application Guideand the Table of Page Limits must be followed.

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

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

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

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

Other Attachments:

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

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

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

1. Download the “VCOC Certification.pdf” at the NIH SBIR Forms webpage. 

2. Answer the 3 questions and check the certification boxes.

3. The authorized business official must sign the certification.

4. 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.

5. 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.

Community Engagement and Research Inclusion (CERI) plan

In an Other Attachment entitled “Community Engagement and Research Inclusion (CERI) Plan”, all applicants must include a summary that proposes or describes how community engagement strategies and community-engaged research will be employed during the planning period; specifically five components, a) communities of interest, b) community partners (if applicable), c) partnership development, d) strategy for incorporation of input, and e) success evaluation metrics. The “Community(ies) of interest” includes people with lived experience (PWLE; lived experience as a member of a health disparity population  (HDP) community(ies)) who have or are at risk of developing neurological disorders.  Community partner(s) include those who represent communities of interest. Our working definition of community partner is a person(s), group, or organization with demonstrated experience leading, advocating, representing, or partnering on behalf of the interest of or perspectives of HDP communities. Examples of community partner(s) include: community champions, key informants, community advisory board, patient advisory board, advocacy organization, community organization, community health worker, FQHC social worker, HDP community faith leader, members of American Indian or Alaska Native tribes, etc. Applicants must describe an existing or proposed partnership that outlines the roles of community partners, the organizational and decision-making structure for the partnerships and the degree of recurring discussions between research team and community partners. Applicants should aim to incorporate input collected through CE strategies in at least two phases within the study: planning/design (i.e., participant outreach, IRB development, advisory board development, etc.), data collection (i.e., culturally appropriate materials, researcher/coordinators/practitioner HDP interviewer style/language, etc.), findings interpretation (i.e., HDP participant research attitudes, cultural context relevant to participant responses, etc.), or communication of findings (i.e., community newsletter, community seminar, health empowerment materials, etc.). Finally, the CERI plan should describe metrics to evaluate and assess meaningful community engagement. The CERI plan may be no more than 2 pages in length and should include a timeline and milestones for relevant components that will be considered as part of the review.

Examples of meaningful community engagement and community-engaged research elements to describe in the CERI plan include but are not limited to:

• Ensuring that community partners and PWLE represent interests relevant to community of interest described within the study
• Proposed roles of academic partners and community partners, including the composition and expertise of the community partners and stakeholders, the phase(s) (i.e., design, conduction, analysis, interpretation, and/or dissemination) of research the community partner will be engaged in, the program infrastructure and management of partnerships (e.g., memorandum of understanding) co-created with or approved by the community partner, if applicable
• Obtaining and incorporating community partner/PWLE input regarding utilization of appropriate linguistic and cultural competence strategies within the study design (e.g., language translation, cultural adaptation) and ensuring representation of participants who have significant social, economic and/or linguistic disadvantage anticipated to participate in study
• Describing how community partner/PWLE will be engaged at specific phases of the research study and a plan for how their input will be incorporated
• Describing plans for regular recurring reflection/topic discussions with community partner/PWLE and how these discussions will serve goals of the project
• Consideration for appropriate and equitable resources provided to community partner/PWLE based on their time and effort spent contributing to the study, as well as mutual benefit and recognition (i.e., publication authorship, conference presentation, work group representation, etc.)
• Outlining methods and metrics to monitor community engagement efforts, including a description of how data will be collected within the framework of the grant activities
• The anticipated or planned personal benefits including dissemination of information during and following the study, knowledge and empowerment of community partner/PWLE

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

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

All instructions in the How to Apply – 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/program manager 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/program manager time

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

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

Research Strategy:

Significance and Biological Relevance: Applicants must 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 must  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 must  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. 

For other studies, such as biomarker studies, the above instructions still apply, and the description should emphasize the specific need and potential impact for diagnosis, therapy development, etc. as appropriate.

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 should 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. 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 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 regard to the scientific rigor guidelines published by NINDS https://grants.nih.gov/. 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 must provide a brief description of their proposed study, including the following:

• A description and rationale for the selected trial design.
• Without duplicating details of the PHS Human Subjects and Clinical Trials Information Form, 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 the next trial phase These should be biomarker-informed wherever possible. 

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

A study protocol synopsis must  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 in section E of the Commercialization plan, "Finance 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 NOFO; (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 NOFO.

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

Resource Sharing Plans:

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

Other Plan(s)

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

• 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.

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 How to Apply – Application Guide; any instructions provided here are in addition to the How to Apply – Application Guide Instructions.

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

All instructions in the SF424 (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.

a. Value of the SBIR/STTR Project, Expected Outcomes and Impact

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 NOFO 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 NOFO advance the product or technology far enough to attract sufficient, independent third-party financing and/or strategic partnerships to carry out full commercialization?

b. Company

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 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) .  

e. Finance Plan

Applicants are expected to provide a Finance 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 third-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 Finance Plan.

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 How to Apply - Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.7 Study Timeline

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

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

Assurance of the protection of human participants and the biohazard safety of employees (if applicable) must be provided for the overall study and for each clinical site. The applicant must discuss any issues which might lead to concern for the welfare of participants. Additionally, the human subjects section of the application must address data security measures and confidentiality.

 Section 4 - Protocol Synopsis (only required for clinical trials)

4.5 Will the study use an FDA-regulated intervention?

Documentation of availability of interventional agent(s) or device(s) as well as plans and support for acquisition and distribution of interventional agent(s) or device(s).

Regulatory Approvals. If the intervention is a drug, biologic, or device, applicants must provide documentation from the FDA providing information on one of the following scenarios:

(a) The protocol has been submitted under an open IND and the IND is not under full or partial hold. Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA.

(b) The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has fully approved the IDE or IDE supplement. Under this scenario, applicants must provide documentation of an IDE or IDE supplement full approval letter from the FDA.

(c) The protocol has been submitted under an IND and is on full or partial hold. Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations. Applicants should discuss how they intend to address the hold issues and when they believe they will have FDA approval to proceed with trial implementation.

(d) The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has conditionally approved the IDE or IDE supplement. Under this scenario applicants must provide full documentation from the FDA on the conditions of approval. Applicants should discuss how they intend to address these conditions and when they believe they will have FDA approval to proceed with trial implementation.

(e) The protocol is exempt from an IND. Under this scenario applicants must provide a copy of the exemption email or letter from the FDA.

(f) The protocol is either exempt from the IDE regulations or does not require IDE approval because it is determined to be nonsignificant risk. Under this scenario applicants must provide either an IDE exemption letter or a copy of the risk determination letter from the FDA.

Delayed Onset Study

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

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

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Information on the submission process and a definition of on-time submission are provided in the How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide.  Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will be withdrawn.

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

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

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. The NeuroNEXT infrastructure (CCC, DCC and clinical sites) 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. While some applicants will be relatively junior in their careers, NeuroNEXT provides a cadres of experienced clinical trial experts who can ensure high quality implementation and oversight of studies. 
 

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

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

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).

Reviewers will consider each of the review criteria below as appropriate for the stage of research, 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 and commercial impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project and proposed product or service address an important problem, a critical barrier to progress, or unmet need 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 and commercialization of the resulting product or service 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? How strong is the described market opportunity in the Commercialization Plan including: (i) the product or service being developed; (ii) target customers; and (iii) how the product will solve a demonstrated customer need?

For a Phase I, does the proposed project have commercial potential to lead to a marketable product or service? 

For Phase II (all types) and Fast-Track applications, does the Commercialization Plan demonstrate a high probability of commercialization? How strong is the described market opportunity in the Commercialization Plan including: (i) the product or service being developed; (ii) target customers; and (iii) how the product or service will solve a demonstrated customer need?)   

Specific to this NOFO:

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?

How well do the community partners and PWLE represent the HDP(s) of interest relative to the study?

How well does the CERI plan include engagement of community partners and PWLE throughout the research process? 

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 the proposed product or service?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project and will they provide a meaningful contribution to successfully complete the proposed aims? Do the PD(s)/PI(s) have appropriate experience and training to lead this project? If so, have they demonstrated an ongoing record of accomplishments in their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? For projects in later stages, does the team have expertise to commercialize the prodcut or service?

Specific to this NOFO:

Are 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. 

If the CERI plan includes community partners as Investigators, how well do their experience and expertise fit the goals of the study and the HDP population(s) of interest? 

In addition, for applications involving clinical trials

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

Innovation

How does the proposed product or service represent an innovative solution to important problem, barrier to progress, or unmet need in research or clinical practice? Does the product or service proposed in application challenge and seek to shift current research or clinical practice paradigms? What meaningful competitive advantages does the end product or service proposed offer over existing approaches, instrumentation, or interventions or those in development?
 

For Phase II (all types) and Fast-Track applications, does the small business present a reasonable plan to create a temporal barrier against other companies aiming to provide a similar solution, including protecting the intellectual property relevant to the product or service being studied or used during the project?

 

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

For Phase I applications, will the strategy establish feasibility, and will particularly risky aspects be managed? Are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

For Fast-Track applications, Are there clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II? Will successful completion of the research aims significantly advance development of the proposed product or service toward eventual commercialization?

For Phase II (all types) applications, will successful completion of the research aims significantly advance development of the proposed product or service toward eventual commercialization? How well does the application demonstrate progress toward meeting the Phase I (or equivalent) objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

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

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

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

Specific to this NOFO:

How well does the CERI plan: 1) Articulate the roles of all community partners/PWLE and provide sufficient resources to reflect their level of engagement? 2) Outline how specific community partner/PWLE input will be incorporated and applied to influence study process or outcomes? 3) Allow community partners to be full participants at various phases of the research process? 4) Describe methods and metrics for evaluating successful community engagement? 5) Describe anticipated personal and research benefits to community partner(s) and PWLE? 6) Describe plans to disseminate information back to the community partners/PWLE and the community as a whole? 7) Describe management of the community partnership or infrastructure to resolve conflict? 8) Incorporate relevant organizations, groups, and/or stakeholders relevant to the study and HDP population(s) of interest? 

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

Will the scientific and business environment in which the work will be done contribute to the probability of success and eventual commercialization? Are the small business 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?

For Phase I applications, does the small business concern have appropriate business expertise and resources, or have they identified appropriate business resources, to accomplish the aims of this project and support commercialization of the proposed product or service?

For Phase II (all types) or Fast-Track applications, does the applicant have access to the business experts and resources needed to accomplish the aims of this project and to commercialize the proposed product or service?

Specific to this NOFO:

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

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

In addition, for applications involving clinical trials

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

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

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

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

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?
• To what extent has the applicant identified their customers and demonstrated a clear understanding of their needs?

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) Protection:

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?

Study Timeline

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)?

Commercialization Plan (Phase II and Fast-Track Only)

For Phase II (all types) and Fast-Track applications, reviewers will consider the following:

How well does the application present the market opportunity, including market segments, that its product or technology will address? Does the applicant understand the barriers to commercialization of its product or service (e.g., regulatory approval, insurance reimbursement, competitive products, customer preferences)? Does the application have appropriate strategies to address these barriers?

Does the application provide appropriate post-SBIR product development and commercialization milestones and explain how these milestones will be achieved? Does the application present a plan for funding the development and commercialization of the product or service? If applicable, did the applicant obtain letters of interest or commitment for such funding and/or resources?

Are the executives, management team, and business experts well suited to advance the development and commercialization of the proposed product or service? If not, is there a plan in place to add the necessary expertise as the product advances towards commercialization?

Is there a sound strategy for driving product adoption and generating revenue from the product or service (e.g., product sales, licensing, partnerships)?

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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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

For Phase IIB Applications, the committee will consider the following:

1) the progress made in the last funding period.

2) the commercial potential (i.e. the probability that an application will result in a commercial product), which may be validated by the applicant's ability to secure substantial independent third-party investor funds (i.e., third-party funds that equal or exceed the requested NIH funds).

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.

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.

Applications with Foreign Components

Reviewers will consider whether work to be performed outside of the United States is thoroughly justified, based on a rare and unique circumstance, and necessary to the overall completion of the project.

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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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.

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Security risk as assessed by the HHS Due Diligence Program

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

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

Disclosure Requirements Regarding Ties to Foreign Countries

SBIR and STTR applicants under consideration for award will be required to submit the U.S. Small Business Administration (SBA) Required Disclosures of Foreign Affiliations or Relationships to Foreign Countries form (referred to as the "Disclosure Form" hereafter), during the JIT process.  Applicants are required to disclose all funded and unfunded relationships with foreign countries, using the Disclosure Form, 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 Section 2.5.1. 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. Applicants that fail to submit a completed Disclosure Form during the JIT process will not be considered for funding. 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. 

Denial of Awards

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, CDC, and FDA 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 their Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. 
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

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

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

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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Defining 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.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff 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.
• Additionally, an agency program official or IC program director 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 recipients and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: A designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

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

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting.  To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting. 

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.

• Final RPPR 
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR)
• SBIR.gov

Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR 200.301.

Disclosure of Foreign Relationships Reporting Requirements

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, CDC, and FDA 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, recipients must request prior approval from NIH for legal actions such as merger, acquisition, and successor-in-interest or any other change in ownership, entity structure, covered individual, or other substantive changes in circumstances no later than 30 days before the proposed change. See NIH Grants Policy Statement 8.1.3 Requests for Prior Approval and NIH Grants Policy Statement 18.5.2.2 Change in Organization Size & Change of Recipient Institution Actions for more details. Disclosure Forms are required for any changes 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, CDC, and FDA 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, CDC, and FDA 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, CDC, and FDA 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.

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

Finding Help Online: https://www.era.nih.gov/need-help  (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

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

Hyun Joo ‘Sophie' Cho, MD
National Institute of Neurological Disorders and Stroke (NINDS)

Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)

Email: [email protected].

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)

Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 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 and STTR 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) SBIR and STTR Policy Directive.