Required Application Instructions

It is critical that applicants follow the 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. 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

A. Overview

This FOA is part of a suite of complementary programs to encourage the translation of research discoveries into new treatments for neurological disorders and stroke (http://www.ninds.nih.gov/funding/areas/translational_research/index.htm) that fall under the NINDS mission. The NINDS Cooperative Research to Enable and Advance Translational Enterprises for Devices (CREATE Devices, http://www.ninds.nih.gov/funding/areas/translational_research/CREATE-Devices.htm) supports milestone-driven projects for the development, testing, and demonstration of therapeutic devices to treat neurological disorders that fall under the NINDS mission.

This funding opportunity will utilize a fast-track U44 cooperative agreement mechanism to support pre-clinical testing to enable an Investigational Device Exemption (IDE) submission or IRB approval for a Non-Significant Risk (NSR) study and the subsequent clinical study. This funding opportunity supports pre-clinical and small clinical studies where the immediate next steps upon completion will be a 510(k)/510(k) De Novo submission or a larger clinical trial that will lead directly to a 510(k)/510(k) De Novo submission. It is expected that changes to the system design informed by the Early Feasibility Study will be minor and not require additional animal testing. Activities that can be supported in this program include implementation of clinical prototype devices, design verification and validation activities, demonstration of preclinical safety and efficacy, pursuit of U.S. regulatory approval for clinical study, and small clinical studies. As applicants must have comprehensive supporting data, innovation will in part be judged on presenting a credible path towards U.S. regulatory submission at the end of the Phase I project period.

The CREATE Devices program for small businesses consists of three Small Business Innovative Research (SBIR) FOAs focused on different device development tracks and applicants should apply to the appropriate track for their technology. Applicants should apply to only one track per project. Projects to enable clinical studies where the immediate next step upon completion of the study is a subsequent full Feasibility Study and a Pivotal trial to support Pre-Market Approval (PMA) or Humanitarian Device Exemption (HDE) are not within scope of this FOA. Such projects - where changes to the system design informed by the Early Feasibility Study will be minor and not require additional animal testing - should instead apply to the 'Translational and Early Feasibility Studies on the Path to Pre-Market Approval (PMA) or Humanitarian Device Exemption (HDE) FOA (PAR-14-299). Projects to enable Investigational Device Exemption (IDE) submission, where the early clinical studies would inform a final device design that would have to go through most - if not all - of the bench-top and preclinical animal testing on the path to clinical trial and market approval, are not within the scope of this program announcement. These projects should apply to the Translational and Clinical Studies to Inform Final Device Design FOA (PAR-14-300).

All projects will have two phases, Phase I and Phase II. The initial Phase I will support preclinical development toward filing of an IDE or obtaining IRB approval for an NSR study. All projects will start at the Phase I but the length of the Phase I will depend on the maturity of the project at entry. Only those Phase I projects that have met specific criteria (see below) will be eligible for transition to the Phase II after NIH administrative review. The Phase II will support a small clinical study. NINDS recognizes the funding in terms of lengths of award and amount is only sufficient to support small clinical studies leading to 510(k) or 510(k) De Novo submission.

The U44 cooperative agreement mechanism is milestone-driven and involves NINDS program staff's participation in developing the project plan, monitoring research progress, and appropriate go/no-go decision-making. NINDS staff will also provide assistance to academic investigators in familiarizing them with the therapeutic device development process and the criteria needed to advance therapeutic leads to the clinic. The expectations of the program are in line with those of industry in regards to advancing therapeutic devices through the developmental pipeline. As such, an inherent high rate of attrition is expected within this program.

Applicants are strongly advised to read through the CREATE FOA Frequently Asked Questions (FAQs) and examples at the website (http://www.ninds.nih.gov/funding/areas/translational_research/CREATE-FAQ.htm). For this funding opportunity announcement phase I clinical testing, studies or trials refer to the common phases of a clinical trial. U44 Phase I and II refer to the project phases of the SBIR program.

B. Scope

Projects must focus on a single disorder that falls within the mission of NINDS.

Devices within the scope of this program are expected to be very close to the 'final system' and manufactured using very close to the same manufacturing process for any subsequent clinical studies and eventual market manufacture. If a subsequent larger clinical study is required for market approval, it is expected that any changes to the manufacturing process or the final system design informed by this small clinical study will be minor, and will not require additional pre-clinical data or clinical data prior to conducting the larger clinical study.

Entry Criteria

For entry to the program, projects should have:

• Comprehensive Supporting Data: Ideally, preliminary proof-of-concept data would be obtained using an in vivo model representative of the intended patient population.
• A compelling case for a successful IDE submission by the end of the Phase I or IRB approval for a Non-Significant Risk (NSR) study at the end of the Phase I.
• Overall device development plan, including when contact with the appropriate regulatory bodies is planned, clinical considerations, and a needs assessment.
• Identified one or more clinically meaningful device outcome measures based on input from both clinicians and patients
• Proposed technology directly on the path to U.S. regulatory approval. The next step should be a 510(k)/510(k) De Novo submission or a larger clinical trial leading directly to a 510(k)/510(k) De Novo submission. Changes to the device and study design after the clinical study will be minor and will not require additional animal testing.
• Non-binding FDA Pre-Submission (formerly pre-IDE) feedback clearly denoting that the proposed pre-clinical testing plan is sufficient to support a successful FDA submission for an IDE by the end of the Phase I. For Non-Significant Risk (NSR) studies, preliminary communications (e.g. letter or other documentation) with the IRB indicating what pre-clinical testing will be necessary to support the NSR clinical study is sufficient.
• If the end-goal of the U44 Phase II is a 510(k) or 510(k) De Novo submission, pre-Submission feedback from the FDA (formerly pre-IDE) indicating that the outlined clinical protocol if successful is likely to lead to a successful 510(k) or 510(k) De Novo submission.
• If the end-goal of the U44 Phase II is a small clinical study to inform criteria for a subsequent larger clinical study to support a 510(k) submission, clear metrics for success must be defined.

U44 Phase I Scope

Examples of studies that can be proposed during the Phase I include, but are not limited to:

• Non-GLP (Good Laboratory Practice) animal studies to develop surgical techniques relevant to the device, define relevant therapeutic parameters, and refine device design in preparation for subsequent GLP testing for regulatory approval
• Bench-top and animal testing to meet FDA Recognized ISO/ASTM Standards
• Activities to become GMP (Good Manufacturing Practice) compliant
• Activities to bring the development process under Design and Quality Systems Control
• Device, software, and firmware design verification and validation activities
• Regulatory affairs
• GLP compliant large animal model safety and/or testing of an implanted device
• IDE submission

U44 Phase II Scope

Phase II will support a small clinical study that will lead to either a 510(k)/510(k) De Novo submission or a larger clinical trial leading directly to a 510(k)/510(k) De Novo submission. It should be noted that clinical studies are only supported for projects where the preclinical activities are conducted under this funding mechanism.

• Examples of Activities Inappropriate for this FOA: Basic research and studies of disease mechanisms
• Animal model development: All in vivo models must have been established and characterized in the applicants or collaborators laboratory.
• Development of diagnostics, or diagnostic devices.
• Rehabilitation strategies.
• Imaging technologies.
• Definitive clinical trials of therapeutic devices, such as a full Feasibility study and/or Pivotal Trial
• Applications without pre-clinical testing or activities Applicants proposing clinical trials or biomarker studies that fall outside of the scope of this FOA may wish to consider applying to the NINDS NeuroNEXT clinical trials program (http://www.ninds.nih.gov/news_and_events/proceedings/20101217-NEXT.htm), the NINDS Exploratory Clinical Trials program (https://grants.nih.gov/grants/guide/pa-files/PAR-13-281.html), or to the NIH StrokeNet program for stroke indications (http://www.ninds.nih.gov/research/clinical_research/NINDS_stroke_trials_network.htm.
• Pre-clinical studies to enable IDE submission, where the early clinical studies would inform a final study design that would require additional pre-clinical testing.
• Pre-clinical studies to enable IDE submission, where the immediate next steps upon completion of an Early Feasibility Study will be a full Feasibility Study and a Pivotal Trial in support of a PMA (Pre-Market Approval) or HDE (Humanitarian Device Exemption), instead of directly leading to a 510(k) submission
• Efforts to develop neurotechnology for fundamental study of the nervous system
• Fundamental basic/applied research projects that employ existing market approved devices for their labeled uses are outside the scope of the present FOA but may be within scope of the Bioengineering Research Grants and Partnerships program announcements (see http://www.ninds.nih.gov/research/bioengineering/).
• Projects focused on neural prosthetic technologies for augmentation of healthy individuals.

Because device development is an inherently high-risk process, it is anticipated that there will be significant attrition as projects move through the device development process. Applications must propose one or more milestones associated with each Specific Aim. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision-making for the project, and should have quantitative criteria associated with them (see Section IV.2 for details).

Prior to funding an application, NINDS program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the NINDS review panel or NINDS program staff. A final set of NINDS approved milestones will be specified in the Notice of Award.

Progress towards achievement of the final set of milestones will be evaluated by NINDS program staff. NINDS program staff may consult as necessary with independent consultants with relevant expertise. If justified, future milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NINDS portfolio balance and program priorities, competitive landscape, and availability of funds.

NINDS encourages increasing the robustness and reproducibility of observed results. In some cases, conducting additional critical experiments will be important for NINDS to have confidence in making a funding decision. Therefore, NINDS program staff may add experiments that need to be conducted prior to or during the award as an additional milestone(s). In most cases, these studies will be supported by additional funds from NINDS.

Phase I/Phase II Transition

An administrative review will be conducted by NINDS program staff, with potential input by NINDS independent consultants to decide on which of the Phase I projects will be transitioned into the Phase II based on the following:

• Successful achievement of the defined milestones for the Phase I of the project
• Likelihood of success in clinical testing
• Competitive landscape
• Program balance
• Availability of funds
• Submission of the IDE for the clinical study with documentation of final or conditional approval of the IDE from the FDA to start the human study or Institutional Review Board (IRB) approval for a Non-Significant Risk (NSR) study
• IRB Approval
• Submission of the final clinical protocol and supporting documents to NINDS for administrative review, and notification of approval by NINDS
• Agreement on updated timeline, milestones and budget for the clinical study

D. Quality and Compliance Requirements

The use of the Design Control and Quality Systems processes (http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm070627.htm) to the degree specified by the FDA is required. Intermediate steps in the Design Control process (e.g. design reviews, design verification, design validation, and design transfer activities) where appropriate, and IDE submission should be represented in the annual milestones. NINDS recognizes that the degree to which Design Controls and Quality Systems processes are required by the FDA may vary substantially depending on the specific device. Investigators are encouraged to discuss these issues with the FDA and regulatory consultants prior to submitting an application so the extent to which these processes are required are clearly defined and verifiable in the application. Applicants should consider Guidelines and Policies for Monitoring Clinical Research in the formation of a plan for data and safety monitoring: http://www.ninds.nih.gov/research/clinical_research/policies/dsm.htm.

Since the ultimate goal of the CREATE program is to bring new therapeutic devices to the market, the program strongly encourages the awardees and/or their collaborators to obtain and retain any IP developed around the device during the project period (see instructions on attachment or letters to address IP issues in Section IV). Recipients of awards are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the device development process. The PD/PI is expected to work closely with technology transfer officials at his or her institution to ensure that royalty agreements, patent filings, and all other necessary intellectual property arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. For rare or ultra- rare diseases where commercialization may be challenging, applicants are encouraged to discuss alternative strategies with NINDS Scientific/Research staff to get further guidance.

As a U44 cooperative agreement, implementation will involve the participation of NINDS program staff in the planning and execution of the projects. Applicants are strongly encouraged to consult with NINDS Scientific/Research staff when planning an application. Early contact provides an opportunity for NINDS Scientific/Research staff to provide further guidance on program scope, goals, and developing appropriate milestones. Applicants should contact NINDS Scientific/Research staff at least 12 weeks before a receipt date.

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

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), 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; 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.

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.

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 receive a new Phase I award. This requirement does not apply to companies that have received 20 or fewer Phase I awards over the 5 year period.

Companies that apply for a Phase I award and do not meet or exceed the benchmark rate will not be eligible for a Phase I 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.

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.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM, SBA Company registry, and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• SBA Company Registry New requirement. See Section IV. Application and Submission Information, SF424(R&R) Other Project Information Component for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a DUNS number to complete this registration. SBA Company registration is NOT required before SAM, Grants.gov or eRA Commons registration.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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

In Phase II, normally, a minimum of one-half or 50% of the research or analytical effort must be 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 generally may not exceed 50% of the total Phase II amount requested (direct, F&A/indirect, and fee).

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.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

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

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

• For this specific FOA, the Research Strategy section is limited to 30 pages.

Instructions for Application Submission

The following section supplements the instructions found in the SF 424 (R&R) SBIR/STTR Application Guide and should be used for preparing an application to this FOA.

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

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

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

Protection of Human Subjects:

Data and Safety Monitoring Plan: Applicants must include a Data and Safety Monitoring (DSM) Plan that is commensurate with the risk level of the proposed clinical trial (see https://grants.nih.gov/grants/guide/notice-files/not98-084.html). For exploratory clinical trials it generally will be acceptable for the data and safety monitoring to be conducted by an investigator-appointed Study Monitoring Committee (SMC), an Independent Medical Monitor (IMM), or, for single-site trials involving low risk, the Program Director/Principal Investigator and his/her IRB. However, NINDS may decide to establish an independent Data and Safety Monitoring Board (DSMB) depending on the score and risk of the trial. Applicants should refer to NIH’s policy on data and safety monitoring (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html) as well as the NINDS Guidelines for Data and Safety Monitoring (http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm).

Other Attachments:

1. SBA Company registry

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

a. Navigate to the SBA Company Registry.

b. If you are a previous SBIR/STTR awardee from any agency, search for your small business by Company Name, EIN/Tax ID, DUNS, or Existing SBIR/STTR Contract/Grant Number in the search fields provided. Identify your company and click Proceed to Registration .

c. If you are a first time applicant, click the "New to the SBIR Program?" link on lower right of registry screen.

d. Fill out the required information on the Basic Information and Eligibility Statement screens.

e. Press Complete Registration on the lower right of the Eligibility Statement screen and follow all instructions.

f. Download and save your SBA registry PDF locally. The name will be in the format of SBC_123456789.pdf, where SBC_123456789 (9 digit number) is your firm’s SBC Control ID. DO NOT CHANGE OR ALTER THE FILE NAME. Changing the file name may cause delays in the processing of your application.

g. When you are completing the application package, attach this SBA registry PDF as a separate file by clicking "Add Attachments" located to the right of the Other Attachments field on the Research and Related Other Project Information form.

For questions and for technical assistance concerning the SBA Company Registry, please contact the SBA at http://sbir.gov/feedback?type=reg.

2. 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.

a. Download the SBIR Application VCOC Certification.pdf at the NIH SBIR Forms webpage.

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

c. The authorized business official must sign the certification.

d. 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.

e. 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.

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

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

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

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

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

Specific Aims: The Specific Aims section should include Aims delineated for each of the U44 Phase I and Phase II stages. A scientific hypothesis is not required.

Research Strategy: The Research Strategy section should include the following subsections:

A. Significance: Clinical Impact and Feasibility, and Overall Device Development Plan

B. Supporting Data for Entry

C. Detailed Plans for Research Strategy (Including Milestones and Timelines)

D. Team Management

A. Significance:

Clinical Impact and Feasibility: Please note that each application should focus on only one neurological disorder or disease within the NINDS mission, even if the device proposed for development could be used for more than one disorder. The target patient population and intended use should guide the design of the device and of the pre-clinical studies.

• Describe the current state of knowledge of the etiology, clinical characteristics, and current and projected prevalence of the proposed disease indication.
• Briefly discuss available treatments, their limitations, and how the proposed project would provide a benefit over existing therapies, regardless of therapeutic class (i.e. agents and devices).
• Identify one or more clinically robust and meaningful device outcome measures based on input from both clinicians and patients.
• Discuss how the proposed project relates to therapy development efforts underway in academia and industry, including both agents and devices.
• Explain the rationale for the minimally acceptable and ideal results. Briefly comment on the feasibility of conducting clinical trials toward these goals (e.g., availability of clinical trial networks).

Overall Device Development Plan: Applicants must include an overall plan for device development. This plan should include:

• A clearly stated device development timeline that includes practical, achievable goals.
• Evidence of contact with appropriate U.S. regulatory bodies (e.g. FDA in the form of Pre-submission meetings and IDE submission).
• Clinical considerations including, but not limited to, the tools and process for device insertion and method for evaluating the functional integrity of the device. This plan will often involve collaboration between the investigators, clinical researchers, and may include the participation of private-sector companies and/or voluntary agencies.
• Needs assessment to establish performance requirements and identify significant issues faced by stakeholders (patients, clinicians, caregivers, customers, regulators, and insurance payers), which is a key step in the design control process and will be evaluated for adequacy.
• NINDS recognizes that early smaller studies are often used to attract investors to support necessary larger studies for market approval. Consequently, investigators will be evaluated on clearly defining metrics for success in the small U44 clinical study in terms of obtaining funding for the necessary larger study to support market approval.

B. Supporting Data for Entry

The Supporting Data for Entry section will contain, but are not limited to, comprehensive data and information that validate the feasibility of conducting studies to address the specific aims. When presenting results, sufficient information must be available about study design, execution, analysis, and interpretation. PD(s)/PI(s) should explain the choice of models or assays, primary, secondary and exploratory endpoints and how they are clinically relevant. PD(s)/PI(s) should consider including blinding, randomization, power analysis for sample size, and independent replication in their application if applicable. Examples of the critical elements of a well-designed study are summarized on the NINDS website http://www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf.

Due to the unique and varied nature of device applications, NINDS recognizes that some concepts outlined in the rigor guidelines such as independent validation and/or fully blinded/controlled studies may be prohibitively expensive and technically problematic to apply in full to device studies. In these cases, applicants are encouraged to use their discretion when applying the individual rigor criteria, and may instead follow the general spirit of these guidelines to submit high quality pre-clinical research.

C. Detailed Plans for Research Strategy (Including Milestones and Timelines)

This section should include plans that will be used to achieve the specific aims and reach the milestones. Each Specific Aim can be accomplished by one or more milestones and these milestones should be described as part of the relevant Specific Aims. For each milestone, provide sufficient details on methods, assumptions, experimental designs, data analysis plan (if the results are quantitatively measured), and specify the quantitative criteria for measuring success and related rationale. Quantitative criteria should be robust and in-line with the state of the art in the field. In the majority of cases, the quantitative criteria for success in the milestones will also be used for making go/no-go decisions and this should be specified. If a milestone is not to be used for making go/no-go decisions, it should be clearly noted and justified. Specify the timeline for each milestone. There should be at least one milestone each year.

Aims and milestones should directly relate to what will be required for FDA submission or IRB approval. The Phase I should focus on those studies needed to inform the FDA pre-submission communications or for IRB approval of an NSR study. Large animal safety studies are often required by the FDA to support an IDE. Applicants should include a large animal GLP safety study conducted on the full-final device system using the final manufacturing process intended to support the IDE. If a large animal safety study is not required by the FDA, or a test of the full final system using final manufacturing processes is not required, applicants should include communication from the FDA clearly stating this is the case.

Study conceptualization and planning must be at a stage sufficient to allow for an assessment of the likelihood of trial success. Description of the clinical study for the Phase II must include:

• A description of the study design and the rationale for this choice.
• A description of the target population, and why it is an appropriate group to address the hypotheses.
• A list of participant eligibility criteria.
• Participant recruitment and retention plans, including a discussion of the availability of participants for the proposed study and the ability of enrollment sites to recruit and retain the proposed number of participants, including women and minority participants. Data supporting recruitment and retention estimates must be provided. Evidence should be provided that relevant stakeholders (e.g., potential participants, referring and treating physicians, patient groups) have sufficient equipoise, consider the question to be important and the study acceptable. This evidence may be supported by letters from stakeholders (e.g., professional organizations or patient groups).
• 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 other data collection approaches (e.g., telephone, mobile devices, or web-based systems) should be considered.
• Discussion of the potential biases in the study and how they will be addressed.
• Statistical Methods: Discussion of sample size and power calculations; study outcome measures; plans for interim and final analyses; methods of bias control; and methods for handling missing data.
• Data Management and Quality Control: Details of efficient data management and methods for monitoring quality; methods for monitoring the quality and consistency of intervention administration; and methods for ensuring participant confidentiality. Applicants are expected to incorporate data elements from the NINDS Common Data Elements (CDE) Project in their data collection forms (see http://www.nindscommondataelements.org/).
• Discussion of the challenges expected in implementing the trial and how these might be overcome.
• Descriptions of the organization of the study and how the trial will be managed; the role of any internal and external committees (e.g., executive committee, endpoint adjudication committee), and the responsibilities and oversight of any central laboratories/reading centers or resource centers.
• A timeline and milestones for completion of key stages of the trial, especially participant accrual.

D. Team Management Plan:

NINDS strongly encourages applicants to form multidisciplinary teams that consist of preclinical and clinical scientists, disease experts, regulatory experts, statisticians, experts in manufacture under Quality Systems/Design controls, and other relevant academic/industry experts. This multidisciplinary team should be able to define the overall device development plan to ensure gaps that need to be filled can clearly be defined and addressed during this funding period, to design the details of the plans and experiments, and to execute the research strategy. Describe how the team will work together (e.g., data generation, reporting of data and integrated review across teams with various disciplines, decision-making, participate meetings with NINDS, communication etc.) over the course of the project (and include letters of support). Indicate the willingness of the PD(s)/PI(s) and key personnel to operate under the cooperative agreement terms and conditions outlined in section VI.2 of the FOA.

Letters of Support: Applicants should include a letter of support from consultants, contractors, and collaborators.

• If applying from an academic institution, include a letter of support from the technology transfer official who will be managing intellectual property associated with this project.
• If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
• If collaborating with a private entity, state if they are agreeing to provide the device or technology, if there is any limit on the studies that can be performed with that device or technology, limitations on sharing of data, and whether licensing agreements are in place.

Resource Sharing Plans: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) SBIR/STTR Application Guide. Investigators should include a brief one-paragraph description of how the final research data will be shared or why data-sharing is not possible. If patent protection is being sought, investigators should explain how data will be shared after patent protection is secured without impeding further research and the development of commercial products from federally funded research.

Appendix: Do not use the Appendix to circumvent page limits. The instructions for the Appendix of the Research Plan are described in the SF424 (R&R) Application Guide,

SBIR/STTR Information

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 the U44 Phase II), which outlines how and when full commercialization can be accomplished. The full commercialization of the product/technology should be carried out with non-SBIR funds.

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

1) Statement of Need

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

• What is the perceived Valley of Death for the product/technology under development?
• To what extent would a possible award under this FOA advance the product or technology far enough to attract sufficient, independent third-party financing and/or strategic partnerships to carry out full commercialization?

2) SBIR/STTR Commercialization History

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

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

3) Intellectual property (IP) strategy:

Use the Other Attachments function to upload this section. Applicants are encouraged to prepare this section of the application in consultation with partnering institution's technology transfer officials, if applicable.

Applicants should describe the IP landscape surrounding their therapeutic device. Applicants should describe any known constraints that could impede the development of their therapeutic device (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent and/or on the market, etc.) and how these issues could be addressed. If the applicant proposes using a device or technology whose IP is not owned by the small business, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address, to the best extent of their knowledge, any questions of freedom to operate. Applicants should include a letter (see Letters of Support) from the entity who owns the IP indicating whether they will provide the device or technology, if there is any limit on the studies that can be performed with that device or technology, and agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.

If patents pertinent to the therapeutic device being developed under this application have been filed, the applicant should indicate the details of filing dates, what types of patents are filed, and application status, and associated USPTO links, if applicable.

Applicants should discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions. Applicants should clarify how IP will be shared or otherwise managed if there are multiple PD/PIs and institutions involved.

Part I. Overview Information contains information about Key Dates. 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.

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.

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.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) SBIR/STTR Application Instructions. 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 Applying Electronically.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) SBIR/STTR Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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 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? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed project have commercial potential to lead to a marketable product, process or service? (In the case of Phase II, Fast-Track, and Phase II Competing Renewals, does the Commercialization Plan demonstrate a high probability of commercialization?)

Specific to this announcement:

Clinical Impact and Feasibility:

If the project is successful, how will it affect clinical practice with consideration to existing treatments and therapeutics development efforts (both devices and agents) underway in academia and industry?

Is the target patient population and intended use guiding the design of the device and the pre-clinical studies, i.e. have they identified one or more clinically meaningful device outcome measures based on input from both clinicians and patients?

If the study is intended to motivate investor support for a necessary larger follow-on study for 510(k) submission, will the proposed study remove key knowledge barriers/defining unknown risks critical for developing a full business case for the therapeutic device?

Overall Device Development Plan:

Is the overall plan for device development reasonable, including the plan after conclusion of the proposed trial?

Is the needs assessment adequate and complete? Does the needs assessment incorporate input from all relevant stakeholders (patients, clinicians, caregivers)? Is there clear metric driven design criteria developed with input from stakeholders?

Investigator(s)

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

Specific to this announcement:

Has an interdisciplinary team been assembled, and have experts in pre-clinical development and clinical development been included in the conception, design, and proposed implementation of the project?

Evaluate the adequacy of the level of expertise and experience of the investigative team for both preclinical and clinical components of the project. Are there any concerns about the investigative group's ability to move the device forward into a trial in humans?

Innovation

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

Specific to this announcement

How significant an advantage does the proposed device offer over all existing approaches as well as those in development for the same indication regardless of therapeutic classes?

If the proposed therapeutic device is trying to improve over early generations that may or may not have been marketed, are the potential advantages truly significant?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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 children, justified in terms of the scientific goals and research strategy proposed?

Specific to this announcement:

Regarding the Section Supporting Data for Entry:

• Does the FDA Pre-Submission (formerly pre-IDE) feedback indicate that the proposed pre-clinical testing plan is sufficient to support a successful FDA submission for an IDE by the end of the UH2 phase? OR For Non-Significant Risk (NSR) studies, do the preliminary communications with the IRB indicate that the proposed pre-clinical testing plan is sufficient to support the NSR clinical study?
• What is the robustness of the unpublished and published data used in support of the application?
• Was it obtained using an in vivo animal model representative of the intended patient population? If not, did the applicant provide adequate justification for the model used?
• Do results from preliminary studies support the feasibility of conducting the proposed specific aims?

Regarding the Section on Detailed Plans for Research Strategy (Including Milestones and Timelines):

• Will the implementation of the overarching plan lead to the development and testing of the proposed therapeutic device?
• Are the proposed experiments designed using rigorous methodological approaches?
• Is the large animal safety study performed utilizing GLP proposed and adequate or is there clear communication from the FDA denoting that a large animal GLP safety study will not be necessary to support an IDE?
• Will the project reach an IDE or IRB approval for a non-significant risk (NSR) study at end of the UH2 phase?

Clinical Study:

• Is the study design complete and adequately described and justified in terms of the goals and any challenges expected?
• Does the study fit with the overall device development plan?
• Is the target population appropriate for the clinical study of the proposed device? Are the inclusion/exclusion criteria, sample size, and power calculations clearly justified and explained in the application?
• Is there adequate consultation with patients and other stakeholders in study design?
• Are the assessments and outcome measures described adequate for the study proposed?
• Are the timelines for completion of key stages of the trial (e.g. participant accrual) realistic and inclusive of necessary steps?

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?

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.

Milestones

Are milestones robust and associated with clear, quantitative criteria for success that allow go/no-go decisions?
Are the timelines proposed for achieving the milestones realistic and inclusive of necessary steps, but also efficient without adding unnecessary steps?
Are there additional key experiments that need to have milestones?

Plans for Patient Recruitment/Retention

Does the application document the following?
Availability of the requisite eligible subject pool in proposed clinical center(s);
The status of evidence showing whether or not clinically important sex/gender and race/ethnicity differences in the intervention effect are to be expected (see Inclusion of Women and Minorities in Clinical Research below);
Are the sites and are the plans presented appropriate for the inclusion of minorities and women?
Plans for recruitment outreach and, as appropriate, follow-up procedures to ensure collection of data at stated intervals; and
Retention plans and practices for anyone who is participating in the trial?

Market, Customer, and Competition

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

Company

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

Intellectual Property (IP)

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

Phase II Applications

Not Applicable

Phase I/Phase II Fast-Track Applications

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

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

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Children

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 children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Phase IIB Competing Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Select Agent Research

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

Resource Sharing Plans

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

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.

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:

• 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.
• Will receive a written critique.

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. 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.

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.

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

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 grantee’s business official.

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

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the U44 cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• The PD(s)/PI(s) will have primary responsibility for defining objectives and approaches, and for planning, conducting, analyzing, interpreting, drawing conclusions on their studies, publishing and sharing the results.
• Awardees are responsible for developing and proposing rigorous milestones that will be achieved during the project period.
• Awardees will retain custody of and have all rights to the data and technology developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Awardees are responsible for pursuing patent protection.
• Awardees are responsible for providing progress reports with completeness that include experimental design with rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not. In cases when NINDS program staff request raw data, awardees agree to provide the data.
• Awardees agree to participate at least once a year in progress meetings (teleconferences) that are organized by NINDS staff.
• Regarding meetings and interactions with regulatory agencies, awardees agree to communicate meeting dates and agenda to the NINDS program staff and invite their participation.
• Awardees agree to communicate study reports from CROs, meeting minutes (and associated data packages if applicable), letters and other forms of communications with FDA, Recombinant DNA Advisory Committee (RAC), and other authorities, and to provide IND# and registration numbers in clinical trial.gov, if applicable.
• Awardees are responsible for providing regulatory and clinical documents that are required for administrative review.
• Awardees must verify that the clinical trial is performed in accord with Good Clinical Practices (GCP) and in accord with NINDS Guidelines for Data and Safety Monitoring in Clinical Trials: http://www.ninds.nih.gov/research/clinical_research/policies/data_safety_monitoring.htm, and must provide data and regular updates to NINDs.

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

• Each project will have the support of one or more Project Scientists from NINDS program staff who are assigned an administrative role for the neurological disorder being studied and have expertise in the implementation of the NINDS Cooperative Program in Translational Research.
• The NINDS Project Scientists will have substantial scientific/programmatic involvement during conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.
• NINDS Project Scientists will provide input on the milestones and make decision regarding finalization.
• NINDS Project Scientists will be responsible for assessing the progress of the projects toward the specified milestones, and for recommending if further funds should be released to the project.
• An important part of the NINDS CREATE program is the coordination of research efforts across different funding mechanisms and research capabilities, and the coordination among efforts aimed at different neurological disorders. NINDS Project Scientists will have the primary responsibility for this overall coordination.
• 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. The assigned program director may also serve as an NIH Project Scientist.
• NINDS Project Scientists will coordinate review of clinical trials by internal NIH clinical and safety experts.
• NINDS leadership will make decisions on project continuation based on program staff recommendations, with program and budget considerations.

Areas of Joint Responsibility include:

Clarifying, negotiating and finalizing the milestones and timelines.

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. Final decisions made by NINDS regarding a discontinuation are not appealable.

NIH requires that SBIR/STTR grantees submit the following reports within 90 days of the end of the grant budget period unless the grantee is under an extension.

• Final Progress Report (requirements have recently changed - please see the NOT-OD-12-152)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR) replaced the Final Cash Transaction Report (PSC 272)
• Phase II Data Collection Requirement for Government Tech-Net Database

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

For details about each specific required report, see the section on Award Guidelines, Reporting Requirements, and Other Considerations, in the SF424 (R&R) SBIR/STTR Application Guide.

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-945-7573
Email: [email protected]

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application , documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
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.

Nick Langhals, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1447
Email: [email protected]

Stephanie Fertig
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
E-mail: [email protected]

Tijuanna DeCoster, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.

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, and P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011). The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.

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