Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title
Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies for Acute Cerebroprotection- Interventions from Small Businesses (U44 Clinical Trial Not Allowed)
Activity Code

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

Announcement Type
New
Related Notices
Funding Opportunity Announcement (FOA) Number
RFA-NS-22-033
Companion Funding Opportunity
RFA-NS-22-003 , U01 Research Project (Cooperative Agreements)
RFA-NS-22-004 , U24 Resource-Related Research Project (Cooperative Agreements)
RFA-NS-22-032 , U01 Research Project (Cooperative Agreements)
Assistance Listing Number
93.853
Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to invite applications for Phase II SBIR applications to test promising cerebrovascular interventions in the NINDS Stroke Preclinical Assessment Network (SPAN). SPAN will facilitate the testing of up to 8 promising cerebroprotective drugs or interventions to be given prior to or at the time of reperfusion in experimental models of ischemic stroke (e.g., transient middle cerebral artery occlusion (tMCAo)). The PIs of the awarded interventions will become part of the network and will collaborate with the SPAN Coordinating Center (RFA-NS-22-004), testing laboratories (RFA-NS-22-003), and other intervention contributors (RFA-NS-22-032) to facilitate the parallel testing of multiple cerebroprotective interventions in experimental models of ischemic stroke. Applicants must propose a research project involving a promising cerebroprotective intervention, supported by rigorous and extensive preliminary data, to be tested in SPAN. If successful, this network will accelerate the identification of the most promising cerebroprotective therapies for future pivotal clinical trials and span the gap between small businesses, preclinical testing laboratories, and a pipeline to clinical testing, in a cost-and time-effective fashion.

This FOA only solicits applications for SPAN intervention research projects from small businesses. Separate FOAs are issued to solicit applications for non-small business cerebroprotective intervention research projects (RFA-NS-22-032), to become a testing laboratory (RFA-NS-22-003), and for the Coordinating Center (RFA-NS-22-004).

Key Dates

Posted Date
January 06, 2022
Open Date (Earliest Submission Date)
February 14, 2022
Letter of Intent Due Date(s)

30 days prior to application due date.

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
March 14, 2022 Not Applicable Not Applicable July 2022 October 2022 December 2022

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

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

Expiration Date
March 15, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts).

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

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

Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this funding opportunity announcement (FOA) is to solicit applications for cerebroprotective intervention research projects from eligible U.S. small businesses to be tested in the NINDS Stroke Preclinical Assessment Network (SPAN).SPAN will support late-stage preclinical studies of putative cerebroprotectants to be given prior to or at the time of reperfusion in rodent models of transient middle cerebral artery occlusion (tMCAo), with clinically relevant long-term outcomes and in models of comorbidities. SPAN testing laboratories (RFA-NS-22-003) will be responsible for the parallel testing of up to 8 selected cerebroprotective interventions that will be chosen from among well-scoring applications submitted under the companion SPAN intervention FOAs (RFA-NS-22-032, RFA-NS-22-033). The overall goal is to determine whether such interventions can significantly improve outcome compared to reperfusion alone and/or extend the therapeutic window for reperfusion, in the hopes of guiding the selection of the best agent(s) to transition to future Phase II clinical trials (to be conducted through StrokeNet). SPAN will consist of one Coordinating Center (CC, RFA-NS-22-004) and up to 8 testing laboratories (RFA-NS-22-003), which will assess up to 8 interventions. The SPAN program will not support any human subjects research.

Background

Until 2015, intravenous recombinant tissue-type plasminogen activator (rt-PA) was the only FDA-approved therapy for acute ischemic stroke. Despite its overall efficacy and safety, rt-PA presents some limitations, such as an increased risk of hemorrhagic transformation, a narrow time window of a few hours from stroke onset, and a low success rate in lysing large clots. Over the past few years, acute endovascular therapy (EVT) with stent-retriever devices and access to advanced imaging modalities have transformed the standard of care for ischemic stroke, offering the opportunity to significantly improve clinical outcomes in selected patients that have salvageable tissue treated as late as 24 hours after their stroke. Unfortunately, despite the success of EVT in clinical trials, many patients still experience neurological deficits following therapy. Thus, there is a critical need to develop adjunctive approaches to improve long-term outcomes after ischemic stroke. These recent advances in stroke treatment such as EVT now offer a new and timely opportunity to further evaluate the potential benefit of cerebrovascular protective agents in the context of mechanical revascularization. Indeed, a cerebroprotectant that can stabilize the stroke penumbra or reduce the rate of infarct core expansion may offer significant benefits if administered as early as possible in a stroke’s evolution.

In 2018, the NINDS launched the Stroke Preclinical Assessment Network (SPAN), the first iteration of which consisted of one coordinating center (CC) and six study sites, each of which proposed a promising neuroprotective modality, all selected following rigorous NIH peer review. The network was designed to perform highly rigorous and reliable preclinical testing with a timeline and resources that would not be possible for a single laboratory, while at the same time allowing a blinded head-to-head comparison of each putative neuroprotective therapy. It also developed a rigorous data analysis pipeline that involves deposition of all raw experimental data from each site into a centralized, secure database followed by randomized assignment of the de-identified data to blinded reviewers at each of the six sites for analysis. During the first funding cycle, the SPAN network successfully demonstrated its ability to test interventions in a time and cost-effective manner. As a result, the NINDS now wishes to build on this momentum by further expanding the network to include more testing sites and promising cerebroprotective interventions.

Research Objectives

The overall goal of this program is to support a preclinical stroke network to conduct late-stage preclinical studies of potential cerebrovascular protective strategies to be given prior to or at the time of reperfusion. SPAN will test in parallel up to 8 compounds/interventions in animal models of tMCAo following the same rigor and methodology characteristic of clinical trials. The parallel testing of multiple interventions, including an adaptive study design that will eliminate compounds that do not demonstrate significant efficacy compared to the others, will allow the identification of the most promising candidates to advance to clinical testing. Only drugs/interventions that are supported by robust and rigorous preliminary data and are likely to be ready for clinical testing by the end of the award will be eligible to be tested through the SPAN network.

Selected SBIR intervention research projects will contribute to these objectives by collaborating with the SPAN Coordinating Center (RFA-NS-22-004) and testing laboratories (RFA-NS-22-003) to provide scientific and organizational leadership for the assessment of their intervention within the network. Small business applications will be expected to propose a detailed research project involving their cerebroprotective agent, with intervention preclinical testing itself then subcontracted to the SPAN testing laboratories via the Coordinating Center. As such, applicants to this FOA will be required to incorporate the SPAN infrastructure into their proposed study.

SPAN Organization

The Coordinating Center (CC) provides scientific and organizational leadership to SPAN to achieve both efficiency and excellence in the implementation and performance of cerebroprotective intervention testing protocols. The CC will work collaboratively with the testing sites, intervention contributors, and the NINDS to provide overall study coordination, including animal enrollment, oversight of study protocols, monitoring of the individual sites, data analysis, data management, data sharing, and reporting. Additionally, the CC will be responsible for the acquisition, formulation, and distribution of active and control compounds. Limited competition for the CC will be proposed through the companion FOA RFA-NS-22-004.

Up to 8 selected cerebroprotective interventions will be tested in parallel in SPAN in a controlled, randomized, and blinded fashion. Such interventions may be proposed by academic, small business, or industry investigators. The proposed interventions should be mature to potentially rapidly advance to a clinical trial at the end of the testing phase. All selected interventions will be assessed by the testing laboratories following standard protocols and procedures, under the direction and leadership of the CC. Candidate compounds/interventions for the network will be proposed through the companion FOAs RFA-NS-22-032 and RFA-NS-22-033 (SBIR) and selected following peer review.

SPAN testing laboratories will conduct tests of selected cerebroprotective interventions that will be chosen from well-scoring applications submitted under the companion intervention RFAs. It is expected that SPAN sites will be academic or other preclinical research laboratories with documented expertise in the tMCAo model of ischemic stroke and relevant comorbidities (e.g., aging, hypertension, diabetes, hyperlipidemia, obesity, etc.). In addition, laboratories must demonstrate expertise in the assessment of clinically relevant, long-term functional outcome measures, with a particular emphasis on small rodent neuroimaging and behavioral testing. It is an absolute requirement that laboratories have extensive access to animal MRI facilities. All applicants must also agree to test multiple interventions in collaboration with the other testing laboratories in a randomized and blinded fashion. Testing laboratories for the network should be proposed through the companion FOA RFA-NS-22-003.

The governing body of the network is the SPAN Steering Committee, appointed by the CC in conjunction with NINDS, that will consist of the PD/PI of the CC, the PD/PI of each of the network’s testing laboratories, the PD/PI of each selected intervention, and NINDS Program staff. The CC will be responsible for managing the logistics of committee activities, such as scheduling, soliciting agenda items, finalizing and distributing agendas, arranging and leading monthly teleconferences, preparing minutes, and making logistic and financial arrangements for annual in-person SPAN meetings, including meeting space, accommodation, travel, per diem reimbursement, etc. The NINDS Director has the right to supersede any decision by the network at any time.

Finally, there is also an independent External Advisory Board, appointed by and reporting to NINDS, which includes basic and clinician-scientists with expertise in cerebroprotection, representatives from pharmaceutical and biotech industry, experts in regulatory affairs, statistics, and clinical trial design, and representatives from the NINDS Stroke Clinical Trials Network (StrokeNet) Steering Committee (to facilitate a potential transition to clinical trials to be conducted in the future, if the intervention is successful in SPAN).

Characteristics, Roles, and Responsibilities of SPAN Small Business Intervention Research Project PIs

Up to 8 selected cerebroprotectants will be tested in parallel in SPAN in a controlled, randomized, and blinded fashion. Research projects may come from academic, small businesses or industry investigators. The proposed interventions should be mature to potentially rapidly advance to a clinical trial at the end of the testing phase. All selected interventions will be assessed by the testing laboratories following standard protocols and procedures, under the direction and leadership of the CC.

Please note that the dissociation of intervention research projects from the testing laboratories themselves is a significant change from the prior SPAN funding period. In the prior cycle, the testing laboratories were also required to propose the interventions that would be tested. In contrast, for this current FOA, while the proposed research project should incorporate SPAN infrastructure in its design, the PI/PD of a successful application will not be performing the intervention testing themselves. The small business research project awardee will be responsible for the synthesis and acquisition of the drugs/interventions, reagents costs, travel to participate in steering committee meetings, etc., while preclinical testing of the proposed intervention will be subcontracted to the network (via the CC). Although all applications must include a subcontract to the CC, they must follow the small business work requirement found in section 3.2.

Applicants must consider the following factors:

  • Proposed interventions to be considered for SPAN need to be supported by extensive and rigorously obtained preliminary data (published and/or unpublished) in a relevant experimental stroke model (tMCAo) in rodents or higher species demonstrating efficacy and the lack of safety concerns. Preliminary data must include the effect of the intervention on both infarct volume and clinically relevant long-term functional outcome measures.
  • Applications must also include information regarding the synthesis and/or acquisition of the drug/intervention, solubility and stability data, quality control, proposed route of administration, and a dose-response study.
  • Applications must include a clear description of the proposed intervention’s mechanism of action (including supporting data). This should discuss target engagement, location of the primary target (i.e., periphery or CNS), as well as penetration into the CNS (if applicable).
  • Applicants to this FOA will be required to incorporate the SPAN network infrastructure into their proposed study, including how their intervention can be efficiently evaluated by the testing laboratories in parallel with other awarded interventions, as well as central coordination and data management through the CC.
  • Small business intervention PIs will budget funds for personnel and the manufacture/acquisition of sufficient amounts of their proposed intervention. They will then be expected to establish a subcontract with the CC, which will be used to support the testing of small business interventions by the partially funded testing laboratories within the network.
  • All applicants funded under this FOA must participate in and accept responsibility for driving the scientific objectives of the network and agree to become active members of the SPAN Steering Committee.
  • Applicants must agree to synthesize and/or procure and ship their proposed compound/intervention to the CC in a sufficient amount to be tested in parallel by the SPAN network in a randomized and blinded fashion. Interventions that appear less efficacious will be removed from further testing, while those that demonstrate stronger efficacy will be prioritized, as appropriate, with the use of an adaptive design. Intervention PIs will be required to continue their commitment to SPAN (i.e., participation on the SPAN Steering Committee, attendance at all SPAN meetings) for the entire duration of the award regardless of the status of their intervention, unless directed otherwise by NINDS and the CC.

In addition to the above, it is also preferable (but not strictly required) that applications also consider the following:

  • Animal toxicity data or human safety data are strongly desirable since the proposed interventions should have the potential to rapidly advance to a clinical trial at the end of the testing phase.

Responsive Applications to this FOA

All applications to this FOA must at a minimum incorporate the following features:

  • Applications are limited to research projects that propose cerebroprotective interventions for acute ischemic stroke in preclinical rodent models of tMCAo.
  • Proposed interventions must be supported by rigorous preliminary data and be sufficiently advanced so that they can potentially move into a clinical trial upon testing completion. 
    • Required preliminary data includes the effect of the intervention on infarct volume and clinically relevant outcome measures such as long-term neuroimaging and behavioral outcomes; dose-response; CNS penetration (if applicable); and target engagement/mechanism of action.
    • Human safety and/or preclinical toxicity data is strongly desirable, but not an absolute requirement.
  • Although awarded interventions will not be directly tested by intervention PIs, applications must incorporate SPAN infrastructure and include a thorough description of how the intervention can be efficiently tested by the network. This must include a recommended animal sample size (supported by a power analysis), intervention dosing and treatment schedule, potential short- and long-term neuroimaging and behavioral outcome measures, and methods of rigorous data analysis that could be recommended to the CC for use within the network.
  • All applications must include a clear statement of PI/institutional commitment to the SPAN network and their willingness to participate in SPAN scientific planning (via the SPAN Steering Committee).

Applications Not Responsive to this FOA

Applications that do not meet the stated scope and requirements of this FOA will be considered non-responsive and may not be reviewed for this FOA. Characteristics of non-responsive applications that are considered outside the scope of this FOA include, but are not limited to, the following:

  • Applications that propose studies that meet the NIH definition of a clinical trial and/or involve human subjects research.
  • Preclinical studies that focus on the investigation of the pathophysiology of stroke, target validation/identification, and/or biomarkers related to a specific cerebroprotective intervention will be considered out of scope for this FOA.
  • Applications that propose a research project involving experimental stroke models other than transient cerebral ischemia will be considered out of scope. Out of scope experimental models would include hemorrhagic stroke, neonatal hypoxia-ischemia/pediatric stroke, cardiac arrest-induced global ischemia models, among others.
  • Pilot studies of cerebroprotection that are in the early-phase or not supported by robust and rigorous preliminary data and/or relevant publications and have potential safety or toxicity concerns will not be supported under this FOA.
  • Applications that propose new infrastructure to join the network as a testing laboratory are out of scope for this FOA. Such applications must be submitted under the companion FOA RFA-NS-22-003.

However, while these topics are non-responsive to this FOA, they are of great interest to NINDS, and applicants are encouraged to contact NINDS program staff to determine the most appropriate funding mechanism for their study.

National Institute of Neurological Disorders and Stroke

The NINDS will be responsible for organizing and providing overall support for the SPAN network. NINDS Program and Grants Management staff will be responsible for the overall management of the SPAN network. In addition to regular grant stewardship, a NINDS Project Scientist will be involved substantially with the awardees as a NINDS partner, consistent with the Cooperative Agreement mechanism.

Applicants are strongly encouraged to consult with NINDS Scientific/Program Staff early during the planning phase of their application (See Agency Contacts, Section VII).

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

Section II. Award Information

Funding Instrument

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

Application Types Allowed
New

Renewal (SBIR Phase II)

New (SBIR Direct Phase II)

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

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon the availability of funds and a sufficient number of meritorious applications.

Award Budget

Application budgets are limited to $300,000 in total costs per year for 3 years.

Award Project Period

The maximum project period is 3 years but the actual funded project period is dependent on reaching specific performance milestones (see Cooperative Agreement Terms and Conditions of Award).

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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

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

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

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

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

    Definitions:

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

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

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

Phase I to Phase II Transition Rate Benchmark

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

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

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

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

Phase II to Commercialization Benchmark

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

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

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

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

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

Foreign Institutions

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

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

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

Required Registrations

Applicant Organizations

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

  • 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. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
    • Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, after obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • SBA Company Registry –See Section IV. Application and Submission Information, “SF424(R&R) Other Project Information Component” for instructions on how to register and how to attach proof of registration to your application package.  Applicants must have a DUNS number to complete this registration.  SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
  • eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

 

 

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

It is preferable that only 1 PD/PI be identified on each intervention research project application.

3. Additional Information on Eligibility

Number of Applications

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 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.

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.

Although multiple applications from a single PI/institution will be allowed for the SPAN intervention U44 and/or testing laboratory U01 FOAs, in order to avoid a conflict of interest, the PI/institution being awarded a SPAN intervention U44 or SPAN CC U24 cannot be awarded a testing laboratory U01.

Similarly, although multiple applications from different PIs at a single institution will be allowed for the SPAN intervention and/or testing laboratory U44/U01 FOAs, in order to ensure network diversity, only one intervention U44 award would be made to any given institution.

Contractual/Consortium Arrangements

In Phase II, normally, one-half or 50% of the research or analytical effort is carried out by the small business concern. The total amount of consultant and contractual arrangements to third parties for portions of the scientific and technical effort is generally not more than 50% of the total Phase II amount requested (direct, F&A/indirect, and fee). While it is expected that the small businesses will subcontract a portion of the budget to the Coordinating Center, it will not exceed 50% of the budget, in accordance with SBIR guidelines.

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 II will be the total of the requested costs attributable to each party, unless otherwise described and justified in “Consortium/Contractual Arrangements” of the PHS 398 Research Plan component of SF424 (R&R) application forms.

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:

span@mail.nih.gov
 

Page Limitations

All page limitations described in the SF424 (R&R) SBIR/STTR Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) SBIR/STTR Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments:

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

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

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

  1. Download the “VCOC Certification.pdf” at the NIH SBIR Forms webpage. 
  1. Answer the 3 questions and check the certification boxes.
  1. The authorized business official must sign the certification.
  1. Save the certification using the original file name.  The file must be named “SBIR Application VCOC Certification.pdf”.  DO NOT CHANGE OR ALTER THE FILE NAME.  Changing the file name may cause delays in the processing of your application.
  1. When you are completing the application package, attach this certification as a separate file by clicking "Add Attachments" located to the right of Other Attachments field on the “Research and Related Other Project Information” form.
SF424(R&R) Senior/Key Person Profile Expanded

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

The PI must be willing to commit a minimum of 1 person month effort to SPAN network activities. It is critical to the success of the SPAN network that the intervention project PIs interact effectively and collaboratively with the CC, the testing laboratory PIs, and with the NINDS.

While the PD/PI does not need to have expertise in all of the following areas, the investigative team as a whole should include individuals with experience in: the rigorous testing of the proposed intervention in preclinical rodent (or higher species) models of transient cerebral ischemia and/or human clinical trials of the intervention of interest; the assessment of short- and long-term stroke outcomes with clinically relevant outcome measures including behavioral testing and advanced neuroimaging; and drug development activities.

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Although applicants to this FOA will not be directly testing the proposed intervention themselves, the aims and hypotheses to be tested should still be clearly stated. Key milestones regarding interactions with the SPAN network, the uniqueness of the team, and the expected outcomes of the project, if successful, can be succinctly described in this section.

Investigator(s): Describe the experience of the investigative team in rigorously testing the proposed intervention in rodent models of transient cerebral ischemia with clinically relevant short- and long-term outcome measures and/or in other larger species. Describe the investigative team's experience in cerebroprotection and drug development activities or clinical trials related to the compound of interest. Describe the team's experience in leading and participating in complex multi-site projects.

Research Strategy

Organize the Research Strategy by Significance, Innovation, and Approach. A Milestone Plan, under separate heading, must be included at the end of the Approach section.

Significance: Describe the rationale and supporting data demonstrating the merit of the proposed cerebroprotective intervention to be given at the time of or prior to reperfusion, as well as its likelihood to prove superior to other interventions. If available, describe existing preclinical toxicity data or safety data in humans (as mentioned above, this is preferred but not absolutely required). Discuss how results of the proposed study (positive or negative) may be explained based on the biological action of the proposed intervention and why the proposed intervention is promising among overall cerebroprotective interventions that have been tested preclinically and clinically. Describe the potential path leading to a clinical trial.

Applicants should describe the full body of evidence being used to support the proposed intervention and should include a plausible biological mechanism, a dose response curve, as well as clinical safety data (if available), which would allow the proposed intervention, if successful in its preclinical testing, to potentially rapidly advance to future clinical trials. Preliminary data and/or published literature demonstrating the feasibility and efficacy of the proposed intervention should be included, and the applicant should specifically address the rigor of the animal studies being used as support (https://www.ninds.nih.gov/sites/default/files/transparency_in_reporting_guidance_508C.pdf). Applicants should also provide compelling evidence that the proposed intervention will reach and/or 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 transient cerebral ischemia.

Specific examples of preliminary data that must be included in this section are:

  • A detailed description of the power calculation used to obtain sample size for the described preliminary data, as well as the methods that were used for randomization, blinding, and other inclusion/exclusion criteria.
  • A description of how sex, age and stroke-relevant comorbidities were incorporated in the experimental design.
  • Drug solubility and stability data, proposed route of administration, dose response, and PK/PD data.
  • Toxicity/safety data, if available.
  • The proportion of animals typically lost in preliminary experiments and expected mortality.
  • A detailed description of the statistical analyses that were used.
  • Citations from the literature supporting the efficacy and safety of the proposed intervention in a preclinical model of transient cerebral ischemia and/or in clinical studies.

Innovation: Describe the cutting edge, clinically relevant, and innovative attributes that the application brings to the field of cerebroprotection in the context of the latest advances in endovascular therapy and acute ischemic stroke standard of care, as well as the overall technical advances and innovative strengths that the application has to offer the network.

Approach: Describe the overall strategy, methodology and analyses that could be used to accomplish the aims of the project using the SPAN infrastructure. Detail the strengths and appropriateness of suggested assays and methodologies used to test cerebroprotection, and whether or not these measures are quantitative, robust, reproducible, clinically relevant and clearly linked to cerebroprotection and functional/imaging outcomes in ischemic stroke. Suggested post-tMCAo timing of the intervention and assessment of outcome measures, including rodent MRI, should be justified. Describe potential problems, alternative strategies and benchmarks for success. The experimental plan should describe relevant biological variables, such as sex and age, and the potential use of ischemic stroke-related comorbidities. It should also include examples of how the proposed intervention can be blinded and a sample size calculation/power analysis (as information for the CC).

Applicants should also provide clear scientific, administrative, and institutional commitments to collaborate with other funded network project investigators/sites and the CC to maximize time- and cost-efficiency of testing the selected interventions.

This section of the application should also include a brief leadership plan that touches upon the following:

  • A brief leadership plan should be presented which identifies how the PD/Pl will collaborate with the Coordinating Center and with other PIs from the testing laboratories and interventions/research projects within SPAN to contribute to the success of the network.
  • The brief leadership plan should include a succession plan with identification of a substitute/back-up PD/PI candidate, if possible, to assure programmatic continuity.
  • Success of SPAN will require strong communication and close collaboration. The application should include a communication plan, which discusses the PIs’ general support of collaborative research and their willingness to participate in a collaborative and interactive manner in all aspects of SPAN.Applicants are encouraged to present prior examples of leadership in a comparably collaborative setting.
  • Applicants should comment on any special expertise or unique strengths they can offer to leadership or collaboration within SPAN.

Milestone Plan: The plan should include yearly, well-defined stage-appropriate milestones for the proposed intervention, with clear go/no-go criteria and a realistic timeline. Some examples are outlined below. Milestones should be unambiguous, quantifiable, and scientifically justified. The final milestone plan is subject to concurrence by the CC and NINDS.

  • Set up the required infrastructure to efficiently communicate and network with the SPAN CC, testing laboratories, and other intervention contributors
  • Gather all required solubility, stability and shelf-life, dose-response, toxicity/safety, brain distribution, PK/PD, and target engagement data to be shared with the CC for testing within 60 days from the date of the notice of grant award
  • Synthesize or acquire the drug/intervention in a sufficient amount required for testing across the network and ship it to the CC within 60 days from the notice of grant award.
  • Establish a timeline for intervention transfer (via MTA) to the CC for testing within the network.
  • Participate in all scheduled SPAN teleconferences and annual meetings
  • Develop all resources and expertise required to serve as a scientific expert for the proposed intervention and to aid with troubleshooting as needed.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan.
  • Applications must include a clear administrative and institutional commitment to data sharing, including strategies and ability to share previously collected intervention raw data, images, and protocols both within the network as well as with other investigators.

Appendix:

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

PHS Human Subjects and Clinical Trials Information
PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

Please notify the NINDS Program Officer by email at span@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are strongly encouraged to consult with NINDS Scientific/Research staff early during the planning stage of their application (see Agency contacts, Section VIII). This early contact will provide an opportunity to clarify the applicant's understanding of NINDS’ goals, policies and guidelines. These discussions also provide important information and guidance on how to develop an appropriate application.

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

Section V. Application Review Information

1. Criteria

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.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field?Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed project have commercial potential to lead to a marketable product, process or service? (In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization?)

Do the supporting data suggest feasibility and efficacy of the proposed cerebroprotective intervention and superiority to other interventions that have been tested preclinically and clinically? Is the proposed intervention supported by extensive and rigorously obtained preliminary data in a relevant animal model of tMCAo and/or human clinical trials? Is there evidence of target engagement and is the mechanism of action plausible for cerebroprotection in the context of brain ischemia/reperfusion? Is it likely that the proposed cerebroprotective intervention will be ready for testing in clinical trials by the end of the award?

Investigator(s)

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

Does the investigative team have published experience in testing the proposed intervention in preclinical models of transient cerebral ischemia? Does the team have expertise in cerebroprotection, drug development, and/or in leading drug development activities or clinical trials related to the compound of interest? Does the team have experience in leading and participating in complex multi-site projects?

Innovation

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

Is the proposed concept timely and does it have the potential to advance the field of cerebroprotection in the context of the latest advances in endovascular therapy and overall standard of care for acute ischemic stroke patients?

Approach

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

Are solubility and stability data for the proposed intervention described? Are dose-response studies included to justify the proposed dose and route of administration? Does the proposed intervention raise any safety or toxicity concerns? Are the assays and outcome measures quantitative, robust, reproducible and clearly linked to cerebroprotection? Is the plan for interaction between the team and the CC clearly described? How appropriate are the outcome measures? Does the application describe inclusion/exclusion criteria?

Is a plausible mechanism of action and biological target for the intervention described and consistent with the putative cerebrovascular protective effect?

Does the application describe randomization, blinding, sample size calculation, and study power?

Does the application include appropriate data management plans and plans for training of site personnel?

Are the milestones well defined and quantitative and do they include clear go/no-go criteria? How will the team collaborate with other funded network projects/investigators and with the CC in a time- and cost-effective manner?

Does the application include clear scientific, administrative, and institutional commitments to collaborate with other network sites, intervention PIs, and with the CC?

How well does the Data Sharing Plan provide a summary of the shared data, a description of the data standards, a plan for the data archiving, and a timeline for data submission to the archive and sharing data with the research community? Is there evidence of institutional concurrence and commitment to the Data Sharing requirements of the SPAN network?

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

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

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

Environment

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

Additional Review Criteria

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

Phase II Applications

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

In addition, the review criteria outlined above under significance will be used to evaluate the application’s suitability for a Phase II award.

Phase I/Phase II Fast-Track Applications

Not Applicable

Protections for Human Subjects

Generally not applicable. Reviewers will bring any concerns to the attention of the Scientific Review Officer.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

Generally not applicable. Reviewers will bring any concerns to the attention of the Scientific Review Officer.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Phase IIB Competing Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process 

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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.

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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

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

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

Report fraud, waste and abuse

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

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

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

  • Participating in the design of experimental approaches and protocols; synthesizing or purchasing the proposed intervention and shipping it to the CC; providing required data (solubility, stability, dose-response, brain penetration, etc.) to the CC.
  • Establishing milestones for the project, in consultation with NINDS program staff.
  • Submitting annual progress reports during the funding period, in a format as agreed upon by NINDS program staff. 
  • Accepting and implementing any other common guidelines and procedures developed for the network and approved by NINDS program staff;
  • Interacting collaboratively with the SPAN CC;
  • Attending network calls and participating actively in all SPAN network activities;
  • Serving as a member of the SPAN Steering Committee;
  • Attending in-person SPAN network meetings (including the initial Kickoff Meeting) once per year organized by the CC with input from the NINDS, the Steering Committee, and the External Advisory Board, and present up to date findings and protocols on ongoing projects.
  • Recipientsare expected to make new information and materials known to the research community not only in the annual network meeting but also in a timely manner through publications, web announcements, reports to NINDS program staff, and other mechanisms.
  • Timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) and Project Leaders are requested to submit manuscripts to the NIH Project Scientist within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate Project Leaders and will require appropriate acknowledgment of NINDS support. Timely publication of major findings is required.

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

NINDS Project Scientist will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NINDS Project Scientist will be to facilitate and not to direct the activities.

NINDS Project Scientist  will:

  • Contribute to the adjustment of research protocols or approaches as warranted;
  • Contribute to developing final milestones for the study;
  • Serve as a liaison between the recipients, the NINDS Advisory Council and the larger scientific community;
  • Serve on committees of the SPAN network as appropriate;
  • Assist in promoting the availability of data and resources developed during this project to the scientific community at large;
  • Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;

Additionally, an NINDS Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. As with any award, even during the period recommended for support, continuation is conditional upon satisfactory progress and collaboration with the other network sites and with the CC.

  • Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award including biospecimen and data sharing requirements.

Areas of Joint Responsibility include:

None. All responsibilities are divided between awardees 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 award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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

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

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

In accordance with the regulatory requirements provided at 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in 45 CFR Part 75 and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

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

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

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

Scientific/Research Contact(s)

Francesca Bosetti, Pharm.D., Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: span@mail.nih.gov

Natalie Trzcinski, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-3860
Email: natalie.trzcinski@nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

Section VIII. Other Information

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

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52, 45 CFR Part 75 and 2 CFR Part 200.

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

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