Part 1. Overview Information

Key Dates

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

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

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

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

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) encourages Small Business Innovation Research (SBIR) grant applications from small business concerns (SBCs) that propose to implement investigator-initiated clinical trials related to the research mission of the NEI. This program provides support for milestone-driven, commercialization-oriented clinical trials and will involve participation of NEI program staff in negotiating the final project plan before award and monitoring of research progress. Applications supported by this NOFO must meet the NIH definition of a clinical trial (see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html) and must be greater than minimal risk trials. As defined in 45 CFR § 46.102, a minimal risk trial is one in which the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

The mission of the NEI is to eliminate vision loss and improve quality of life through vision research. Applications considered for funding by the NEI must align with the NEI Strategic Plan.

Background

This NEI SBIR Cooperative Agreement (U44) for Clinical Trials is designed to support SBIR grant applications specifically from small business concerns (SBCs).  Currently, the NEI uses U01 cooperative agreement mechanism https://grants.nih.gov/grants/guide/pa-files/PAR-22-149.html to support early-stage, small-scale clinical trials that are greater than minimal risk; and UG1 https://grants.nih.gov/grants/guide/pa-files/PAR-21-041.html to support large-scale, multi-center clinical trials, human gene-transfer and stem cell therapy trials, and other complex or high resource- or safety-risk clinical trials.

Scope

The scope of this NOFO is to support U44 applications for clinical trials to investigate the safety and/or efficacy of screening, diagnostic, preventative, or therapeutic interventions for eye diseases or disorders. Applicants seeking a Phase II or Phase IIB award must have received an eligible predicate award that is appropriate and relevant (e.g., pre-clinical studies, planning activities, etc.) to this NOFO. An application without an eligible predicate award must be submitted as a Direct to Phase II application. This NOFO is specifically intended for early-stage clinical trials with greater than minimal risk that meet all of the following criteria:

• Include strong preliminary and/or pre-clinical data
• Are early-stage clinical trials
• Have a well described Commercialization Plan (see Section IV for details)

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

• Evaluate and optimize the dose, formulation, safety, tolerability, or pharmacokinetics of an intervention in healthy volunteers or the target population.
• Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity, target engagement, dose-response trends, pharmacodynamic response) in a human “proof of concept” trial.
• Select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, biological activity, or preliminary clinical efficacy.
• Determining the optimal outcome measure (endpoint), its variability, and/or the optimal timing of outcome evaluations in the context of the intervention.
• Establish proof-of-principle and optimize techniques, operation, and usability of a device, inform the final device design decisions, and estimate the magnitude of treatment effects.
• Collecting information on the utility of questionnaires, rating scales, or biomarkers.

This NOFO will support the conduct, completion, and analysis of a clinical trial, including activities related to the conduct of the clinical trial, which include but are not limited to the following:

• training of study personnel
• enrollment and recruitment of study subjects
• investigational product costs
• data collection, management and quality control
• laboratory work and data analyses
• study management and oversight
• establishment of committees to manage the complexity of the trial
• preparation of the final study report and other related post-trial activities
• regulatory activities and site monitoring can be covered if required

Clinical trial planning activities should be completed prior to the time of application submission and investigators must be ready to implement the proposed trial at the time of award. If the proposed clinical trial involves the use of a drug or a device that has not been approved by the FDA for the proposed investigational use, then evidence of an Investigational New Drug (IND) application or an Investigational Device Exemption (IDE) application submission to the FDA that meets all requirements under 21 CFR 312 is required at the time of the U44 grant application submission. It is the responsibility of the applicant to provide evidence from the FDA if an IND or an IDE is not required. NEI reserves the right to deny or postpone the award until evidence of IND/IDE authorization from FDA is provided.

Milestones

Delineation of milestones is a key characteristic of the NEI Cooperative Agreement (U44) for Early-Stage Clinical Trials with greater than Minimal Risk. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity. See Section IV. Application and Submission Information for more specific instructions.

Applications Not Responsive to this NOFO:

The following types of activities remain outside of the scope of this NOFO, and applications proposing such activities will be considered non-responsive to this NOFO and will be withdrawn without review:

• Applications that do not meet NEI Mission: https://www.nei.nih.gov/about/strategic-planning
• Applications involving a clinical experiment that is not directly intended to evaluate a screening, diagnostic, preventative, or therapeutic intervention
• Applications that aim to test a drug, a device, or service with limited or no commercialization potential
• NIH-defined clinical trial applications proposing only mechanistic and/or minimal risk studies
• Applications that are large-scale, multi-center clinical trials, human gene-transfer and stem cell therapy trials, and other complex or high resource clinical trials
• Applications that propose a project that extends beyond a three-year project period
• Applications that propose animal studies
• Applications that lack appropriate attachments (See Other Attachments in Section IV. Application and Submission Information)

Data Monitoring and Safety Committee (DSMC)

A DSMC is required for this mechanism. The DSMC is an independent group composed of individuals not directly involved in patient care or data collection for the study who are responsible for safeguarding the interests of all trial participants, assessing the safety and efficacy of the treatment during the trial, and for monitoring the overall conduct of the trial. The DSMC operates under the guidance of an approved Charter.

Do not name individuals for the DSMC but include areas of expertise that will be pertinent in forming this committee. NEI reserves the right to specify the requirements for the establishment of a DSMC (Data and Safety Monitoring Committee). Applicants are encouraged to discuss those decisions and requirements with NEI prior to submission of the application.

Programmatic Oversight

NEI program staff will closely monitor progress in meeting the milestones of all projects funded by cooperative agreements under this NOFO and will also oversee the management and reporting of adverse events and have regular communications with the PD(s)/PI(s). The NEI Program Official(s) will participate in the DSMC meetings and will serve as a technical representative to the DSMC.

Applicants are strongly encouraged to contact Scientific/Research staff as plans for an application are being developed (see Section VII, Agency Contacts), and no later than 12 weeks prior to the anticipated application submission date.

All research and development activities associated with awards made under this NEI SBIR Cooperative Agreement for Early-Stage Clinical Trials with Greater than Minimal Risk (U44) NOFO must be performed within the United States (the United States is defined as the 50 States, the territories and possessions of the United States, the Commonwealth of Puerto Rico, the Federated States of Micronesia, the Republic of Palau, the Republic of the Marshall Islands, and the District of Columbia).

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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

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

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

3.

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.
 

Performance Benchmark Requirements

Phase I to Phase II Transition Rate Benchmark: In accordance with guidance from the SBA, the HHS SBIR/STTR Program is implementing the Phase I to Phase II Transition Rate benchmark required by the SBIR/STTR Reauthorization Act of 2011 and the SBIR and STTR Extension Act of 2022.The benchmark establishes a minimum number of Phase II awards the company must have received relative to a given number of Phase I awards received during the 5-fiscal year time period. The Transition Rate is calculated as the total number of SBIR and STTR Phase II awards a company received during the past 5 fiscal years divided by the total number of SBIR and STTR Phase I awards it received during the past 5 fiscal years excluding the most recently completed year. The Transition Rate requirement, agreed upon and established by all 11 SBIR agencies, was published for public comment in a Federal Register Notice on October 16, 2012 (77 FR 63410) and amended on May 23, 2013 (78 FR 30951).

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

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

Phase II to Commercialization Benchmark: In accordance with guidance from the SBA, the HHS SBIR/STTR Programs are implementing the Phase II to Commercialization Rate benchmark for Phase I applicants, as required by the SBIR/STTR Reauthorization Act of 2011 and the SBIR and STTR Extension Act of 2022. The Commercialization Rate Benchmark was published in a Federal Register notice on August 8, 2013 (78 FR 48537), with a reopening of the comment period published on September 26, 2013 (78 FR 59410).

• For companies that have received more than 15 Phase II awards from all agencies over the past 10 fiscal years (excluding the two most recently completed fiscal year): Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0.15 (15%) patents per Phase II award resulting from these awards during the past 10- fiscal year period. Applicants that fail this benchmark will not be eligible to apply for New Phase I, Fast-track or Direct Phase II (if applicable) awards for a period of one year. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently completed fiscal years.

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

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

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

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

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement 2.3.9.2 Electronically Submitted Applications for additional information.

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

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

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

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

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

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

For the STTR program, the PD(s)/PI(s) may be employed with the SBC or the single, “partnering” non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration The primary employment of the PD/PI must be with the SBC or the Research Institution (where they are PD/PI at) at the time of award and during the conduct of the proposed project. Each PD/PI must commit a minimum of 10% effort to the project.

The How to Apply – Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the How to Apply – Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, 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, NIH Grants Policy Statement 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

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

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

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

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

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.

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the SBIR/STTR (B) Instructions in the How to Apply – Application Guide, except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the 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:
Brian Hoshaw, PhD
Telephone: 301-402-0566
Email:brian.hoshaw@nih.gov

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

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

All instructions in the 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:

Facilities & Other Resources

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

Other Attachments:

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

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

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

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

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

3. The authorized business official must sign the certification.

4. Save the certification using the original file name.  The file must be named “SBIR Application VCOC Certification.pdf”.  DO NOT CHANGE OR ALTER THE FILE NAME.  Changing the file name may cause delays in the processing of your application.

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

Clinical Protocol (required)

A full clinical protocol must be included. The FDA and NIH developed a Clinical Trial Protocol Template (Seehttp://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/clinical-research-policy/clinical-trials) that can be modified for any type of clinical trial.

The filename "ClinicalProtocol.pdf" must be used and will be reflected in the final image bookmarking for easy access to reviewers.

Manual of Procedures (MOP) (optional)

A MOP may be submitted to include basic elements including, but are not limited to, visit schedule; examination and testing procedures; expected adverse events; study publication policies, draft Informed consent forms (ICFs) and, if applicable, assent form(s); sample data collection forms; data capture, management, quality assurance and analytical procedures; and applicable clinical center information.

The filename "MOP.pdf" must be used and will be reflected in the final image bookmarking for easy access to reviewers.

Interventional Agent(s) or Device(s) Availability (required)

In addition to the information requested in the PHS Human Subjects and Clinical Trials Information Instructions, if the intervention is a drug, biologic, or device, applicants must provide documentation from the FDA providing information on one of the following scenarios:

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

(b) The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has fully approved the IDE or IDE supplement. Under this scenario, applicants must provide documentation of an IDE or IDE supplement full approval letter from the FDA. The IDE or IDE supplement is required to be specific for the clinical trial protocol proposed (e.g., design, sample size, population, device model, etc.) and correspond with the FDA approval. Collation of multiple IDE supplement approvals for different components of the protocol is not adequate.

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

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

(e) A pre-submission has been submitted for FDA advice on the protocol design and intervention. Under this scenario, applications must provide the FDA response and discuss how they intend to address issues identified related to the safety, design, and implementation of the protocol.

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

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

Note: Do not include the IND/IDE application, manufacturer’s product specifications, study protocol, or protocol amendments in this attachment

The filename "FDADocumentation.pdf" must be used and will be reflected in the final image bookmarking for easy access to reviewers.

Data Management, Quality Assurance and Monitoring Plans (required)

This document must provide details of data management, quality assurance and monitoring plans. The description must include but is not limited to the following: methods of data entry, management procedures and systems; data coordination; data storage and security; personnel training and certification procedures; plans for handling deficiencies; participant safety monitoring including activities of the data and safety monitoring committee; appropriate oversight over the conduct of the trial including at a minimum the appropriate clinical monitoring independent of the study team, safety monitoring, regulatory submissions and compliance and quality management; policies and methods for ensuring masking of study results; data confidentiality and participant privacy; preparation of study reports and meeting minutes; other data quality control and monitoring; and, the process for locking the final dataset and sharing results.

The filename "DataManagement.pdf" must be used and will be reflected in the final image bookmarking for easy access to reviewers. This attachment must not duplicate information already addressed in “MOP.pdf” attachment.In addition to this "Data Management, Quality Assurance and Monitoring Plans (required)" section, a Data Management and Sharing Plan (DMS Plan) in the Other Plan(s) section must be included in compliance with the NIH DMS Policy. Each plan should be complete on its own, with (1) the DMS Plan addressing data management and sharing activities for scientific data generated under this NOFO; and (2) the Data Management, Quality Assurance and Monitoring Plans addressing the sharing of clinical results.

NEI Involvement Statement:

Applicants must provide a statement acknowledging and agreeing to NEI staff post-award involvement in conducting the aforementioned types of clinical research studies and must describe plans to accommodate this involvement.

Applications that lack appropriate attachments are incomplete, will not be reviewed, and will be withdrawn.

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.

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

SBIR/STTR Information Form

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

Specific Aims: Concisely state the goals of the clinical trial and the expected outcome(s). Clearly and succinctly present the specific objectives of the clinical trial, including specifying the primary and major secondary endpoints to be measured. Provide a clear explanation of the importance of various endpoints.

Research Strategy: Present an overview of the state of the science, current status and relevance of the trial, discussion of the clinical protocol, and relevance to the research mission of the NEI. Propose a hypothesis-driven clinical trial, and show that the clinical trial is ready for implementation at the time of award. Describe the clinical trial stages, criteria for completion of the stages and contingency plans for each stage to accommodate any anticipated impediments that could require a revision in the timeline.

The Research Strategy should discuss, address, and/or summarize the following:

• Prior Studies and Rationale for Development: The major findings of the pre-clinical and clinical studies that led to the proposed clinical trial should be presented. Data from pre-clinical and pilot studies demonstrating the need for and the feasibility of the trial should also be presented. Discuss how conceptualization and planning have progressed to a stage sufficient to allow for an overall assessment of the likelihood of trial success. Indicate the significance of the problem being studied, the need for the trial, and the potential impact of the results of the trial, including adequate definition of the study objective(s) and how well the clinical trial will test the hypothesis(es) proposed;
• A justification of the intervention and/or study agent(s) to be tested and the protocol to be followed in each arm of the trial;
• Plans for acquisition and handling of study agent(s);
• For proposed mechanistic studies: Discuss the feasibility of the approach(es) and how these studies contribute to the understanding or treatment of the disease/condition;
• For proposed multi-center clinical trials: Discuss the methods for ensuring adherence to the clinical protocol, and standardization and quality control of distribution of study agent(s) and data collection;
• A description of the plans to implement and monitor Good Clinical Practices (GCP), Good Clinical Laboratory Practices (GCLP) and Good Manufacturing Practices (GMP), as appropriate; and
• Demonstrated consideration of ethical issues involving the disease/condition under study.
• In addition, discuss activities related to the conduct, completion, and analysis of the clinical trial
• Any anticipated impediments that could require a revision in the timeline must be identified and accompanied by a discussion of alternative approaches.

Milestones (Required – 1-2 page max):

Delineation of milestones is a key characteristic of the NEI Cooperative Agreement (U44) for Early-Stage Clinical Trials with greater than Minimal Risk. A milestone is defined as a scheduled event in the project timeline, signifying the completion of a major project stage or activity.

The proposed milestones must include achievable goals for the project as follows:

• Completion of start-up activities as applicable (finalization of protocol, completion of any final regulatory approvals, contracting of sites, registration in ClinicalTrials.gov, etc.)
• Enrollment of 25%, 50%, 75% and 100% of the projected recruitment
• Completion of data collection
• Completion of primary and major secondary endpoint analyses
• Publication of primary outcome manuscript(s)
• Preparation of final dataset for public use and data sharing
• Reporting of results in ClinicalTrials.gov
• Contingency plans to accommodate anticipated impediments that could require a revision in the timeline
• A separate attachment with the filename "MilestonePlan.pdf" should be used and will be reflected in the final image bookmarking for easy access to reviewers. The milestones will undergo peer review and will be incorporated into the terms of award.

Gantt Chart (Required – 1-page max):

Applications that exceed this limit or do not include this attachment will be withdrawn. This separate attachment should be entitled "Gantt.pdf". Applicants should include a project timeline in the form of a Gantt chart (or similar) that includes all major tasks to be performed during the project. The chart should also include estimated start and completion dates for those tasks.

Long-term Care Plan for Patients (Required – 3 pages max):

Applications that exceed this limit or do not include this attachment will be withdrawn. This separate attachment should be entitled "Long-term Care.pdf". First, applicants that test implanted devices or biologics should describe the anticipated care needs of participants after a trial has ended, which are related to their trial participation (e.g., continued access to the device, device maintenance, and/or device explant). Where relevant, it is recommended that applicants consider various post-trial scenarios, such as trial failure or success, regulatory approval options, and decisions by device manufacturers to commercialize or discontinue a product. Second, applicants must describe a plan for the care of patients at the end of the study and after the study period, if appropriate. related to the potential care needs. These plans may vary from project to project, depending on, for example, whether patients are likely to have other ways to access this care, the anticipated risks and benefits of receiving this care, the anticipated risks and benefits of not receiving this care, and the feasibility of facilitating this care. All plans should include information regarding post-trial obligations.

Letters of Support: Provide letters of support to document access to or commitment of critical resources, including consortium/site participants, cores, laboratories, pharmacies, data management resources, or other collaborators, including cost-sharing by NIH resources in the case of intramural collaborators. Investigators are referred to https://www.niaid.nih.gov/research/intramural-collaboration-extramural-funded for additional guidance on Intramural Scientist Collaboration on Extramural Funded Grants. In addition, if co-funding or in-kind support is planned from non-NIH sources, include letter(s) of commitment (e.g., type, amount and source of support), signed by a business official.

Appendix:

Note that 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.

The following modifications apply:

Include the informed consent form(s) and, if applicable, assent form(s).

SBIR/STTR Information

Program Type: Check "SBIR" regardless of whether the Phase I or II predicating the application was a SBIR or STTR award.

Commercialization Plan: All applicants are expected to describe a realistic plan, 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?

Why is additional government funding critically needed to accelerate the development of the product or technology toward commercialization? Specifically, what activities are being proposed under this NOFO that would not otherwise be possible through independent third-party investments OR would be significantly delayed without additional NIH support?

To what extent would a possible award under this NOFO advance the product or technology far enough to attract sufficient, independent third-party financing and/or strategic partnerships to carry out full commercialization?

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) Project Management Plan

Applicants must provide a Project Management Plan detailing how the research and commercialization plans will be kept on track. The plan should include specific milestones for the commercialization of the product.

4) Regulatory Plan

If applicable, applicants must provide a regulatory plan describing the regulatory pathway that is being or will be pursued and a timeline for achieving regulatory approval with discrete milestones. Applicants must also submit evidence that they have contacted the appropriate regulatory authority and that their research plan and objectives follow the relevant requirements or guidance of that authority. Examples that provide evidence of appropriate interactions are letters or emails between the company and the appropriate FDA Center personnel or meeting minutes concerning a pre-submission meeting or regarding a 510(k), IDE, PMA, HDE, BLA, IND, or NDA application. Copies of these letters, emails or minutes should be attached in the Letters of Support section in the PHS398 Research Plan form. Applicants may also provide details of their interaction with the regulatory authority in the description of their Regulatory Plan. This should include the regulatory authority contact and date of interaction. Applicants should describe any outside assistance they have obtained or plan to obtain for developing and achieving the proposed Regulatory Plan.

5) Fundraising Plan

The NIH considers the raising of independent third-party investor funds to be an important means to facilitate and accelerate the capital-intensive steps that are required to commercialize new products/technologies emerging from NIH-funded SBIR/STTR Phase II projects. Applicants are expected to provide a Fundraising Plan, which should be a detailed and specific plan for securing substantial, independent third-party investor funds if they are necessary to bring the product to commercialization. If they are not needed, the company should detail how they are able to bring the technology to market without the use of third-party investor funds.

Answer questions 9 and 10as specific to the SBIR program. If the applicant has received SBIR/STTR awards issued by NIH or any other Federal Government agency, attach a file that includes for each SBIR/STTR award: (1) name of awarding agency; (2) award number and date; (3) amount of award; (4) title of project; (5) source, date, and amount of Phase III funding agreement; and (6) commercialization status of each Phase II award.

Resource Sharing Plans:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Other Plan(s)

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

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

Appendix:

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

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

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Projects proposing Delayed Onset Studies will not be accepted under this NOFO.

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the 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 provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. 

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.

In addition, for this PAR, applicants may submit a 1-2 page document providing update on the clinical trial as post-submission materials, up to 30 days prior to the review meeting. This update could include information on clinical sites recruited, obtaining the drug, access to the device, FDA and other regulatory approvals, IRB approvals, and recruitment of key personnel.

Section V. Application Review Information

1. Criteria

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

For this particular NOFO, note the following:

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

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

Reviewers will consider each of the review criteria below 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.

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.

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.

2. Review and Selection Process 

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Eye Institute, in accordance with NIH peer review policies and practices, 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 NOFO.

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

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

Disclosure Requirements Regarding Ties to Foreign Countries

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

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

Denial of Awards

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

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

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" (JIT) information from the applicant as described in the NIH Grants Policy Statement. SBIR and STTR applicants under consideration for award will be required to submit the SBA U.S. Small Business Administration (SBA) issued the Required Disclosures of Foreign Affiliations or Relationships to Foreign Countries form during the JIT process. Applicants that fail to submit a Disclosure Form will not be considered for funding.

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.6. 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 NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

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

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

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

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

2. Administrative and National Policy Requirements

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:

• Federalwide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the HHS Office for Civil Rights website.

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

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 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.”

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

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

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

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

• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
• Defining objectives and approaches, and planning, conducting, analyzing, interpreting, drawing conclusions from and publishing trial results. The design, methods, and procedures of the clinical trial will be detailed in a recipient-prepared and maintained, study-adopted Manual(s) of Procedures and the recipients will have the responsibility for following the protocol
• Ensuring that study progress, quality and safety reports are prepared and distributed as requested by the medical monitor or Data and Safety Monitoring Committee (DSMC). Ensuring that there is formal documentation of all medical monitor safety reviews, or DSMC deliberations, as applicable. This documentation will clearly list all recommendations and explicit action items and will be reviewed and approved by the medical monitor or quorum of DSMC members as applicable. It is the responsibility of the PD/PI to ensure that their responses to safety or oversight monitoring recommendations or action items are formally reviewed and approved by the medical monitor or quorum of the DSMC. The PD/PI is responsible for ensuring that there is proper administration of applicable medical monitoring and/or management of the Committee. The PD/PI must give all medical monitors or DSMC members the name and contact information of the responsible NEI program director and advise them to contact the NEI program director directly with any concerns about the adequacy of trial safety or study implementation, as applicable. In addition, the trial PD/PI must officially notify the NEI program director within 24 hours whenever the medical monitor or DSMC makes a recommendation to substantively modify or stop the study.
• Ensuring that the NEI and the medical monitor or DSMC receives study progress and safety reports as requested.
• Ensuring that the DSMC receives a copy of the study’s primary manuscript(s) for review and approval in advance of journal submission.
• Implementing DSMC recommendations -Timely implementation of substantive DSMC recommendations is expected.
• Notifying the NEI program director within 24 hours of any FDA regulatory actions including: clinical hold; requests for modification; or termination for trials requiring regulatory approval.
• Reporting details of the safety monitoring process in the grant’s annual non-competing renewal (also called RPPR). Specifically, the renewal must note: 1) actual dates for all medical monitor or DSMC meetings as applicable; 2) verification that monitoring minutes have been reviewed and approved by the medical monitor, or quorum of DSMC and, 3) an update on the status of monitoring and general medical monitor or DSMC action items. Note: status reports must not contain any confidential study data or patient information. NEI guidelines for Data and Safety Monitoring of Clinical Trials can be found at: https://www.nei.nih.gov/grants-and-training/policies-and-procedures/guidelines-data-and-safety-monitoring-clinical-trials
• Documenting progress toward the stated study timeline and milestones as specified in the grant application and/or as modified during pre- or post-award negotiations. Specifically, the annual non-competing renewal must include but not be limited to: 1) actual dates of regulatory approvals if applicable; 2) date of enrollment of 1st study participant; 3) date of ClinicalTrials.gov registration, if applicable; 4) enrollment completion date; 5) date of completion of participant follow-up; 6) date of ClinicalTrials.gov results reporting, and, 7) date of initiation of data sharing.
• Reporting on compliance with NIH policies related to the study. Specifically, for clinical trials, the RPPR must note the status of or compliance with 1) registration on ClinicalTrials.gov (i.e., by providing the clinicaltrials.gov identifier); 2) submission of summary results information on clinicaltrials.gov; 3) Relevant NIH trainings (e.g., GCP, human protection, etc.) for applicable study personnel; 4) data sharing; and 5) public access.

The PD/PI is responsible for the overall conduct of the clinical trial and for providing scientific, technical, and administrative leadership to the study. They will have lead responsibility for planning and directing all phases of the study and for using the study's resources. The PD/PI is usually the individual who developed the idea for the clinical trial and is the leader in preparing the Manual of Procedures and organizing the study components.

"PD/PI are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols (including the NIH DMS Policy) and consistent with any approved DMS Plan if awarded."

Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NEI/NIH. The PD/PI must ensure that trial publications are entered in Clinicaltrials.gov by including the registered ClinicalTrial.gov “NCT number” to all trial publications.

Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement of study resources, citing the name of the study or NEI support, or special access to study results, data, findings or resources requires notification and concurrence by the NEI. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by the NEI.

As applicable, any therapeutic agent manufactured using NEI grant support is reserved for either 1) the sole use of treating participants enrolled in the NEI supported trial or 2) laboratory work attending: study product manufacture, repackaging and distribution; quality assurance (i.e. identity, potency, or other aspects of product integrity); and participant safety. Any alternative use of study product requires the express approval of the NEI.

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

NIH Responsibilities:

An NIH Program Director, serving as Project Coordinator, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The appropriate NEI extramural Program Director from the Division of Extramural Science Programs whose name appears on the Notice of Grant Award (NoA) will:

• Nominate members of an independent Data and Safety Monitoring Committee (DSMC). The DSMC membership will be based on recommendations from the Study Leadership and NEI program staff. Assist the PI/PD, in assuring that participant information handbooks, recruitment information, press releases, and publicity exhibits are properly prepared, approved and disseminated.
• Assist the PI/PD in the identification of additional participating clinics, if necessary, to enhance patient recruitment.
• Assist the PD/PI Study Leadership Committee in site visits and routine performance monitoring of the entire study including matters of quality control, within and among various components, and in the determination of inadequate patient recruitment or failure to comply with the protocol. on the part of individual clinics or study core centers. The NEI Program Director will attend and participate in study meetings as appropriate.
• Assist the PI/PD in the preparation and review of study results for publication.
• Assist the DSMC as an expert resource in their evaluation of safety, efficacy, quality, and progress on an ongoing basis, as applicable. Serving as a steward of federal funds, the NEI Program Official will assist but not direct deliberations and decisions of the Committee, e.g., proceeding from one phase of the study to the next; implementing protocol changes, evaluating study progress and quality including patient recruitment, overall clinical and resource center performance; monitoring study timeliness and progress toward meeting milestones, approving ancillary studies, planning data analysis; releasing unmasked data; announcing study findings; determining the timing of release of any interim or final reports; and, reviewing primary outcome manuscript(s) prior to journal submission.
• The NEI reserves the right to curtail, withhold, or terminate support for the study, for an individual award, or support for a participating consortium, in situations involving: inadequate progress toward meeting study milestones including those related to: availability and regulatory approval of study product as applicable, patient recruitment, follow-up, data reporting, or quality control; a major breach of the study protocol or NEI/NIH policy; a substantive change in the agreed-upon protocol to which the NEI does not agree; statistical evidence that the major study endpoint has been reached ahead of schedule; or, human subject ethical issues that dictate a premature termination. Prior to taking such actions, NEI will consult with and receive recommendations from the DSMC. Additionally, the NEI Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Data and Safety Monitoring Committee (DSMC)

The DSMC is an independent group composed of individuals not directly involved in patient care or data collection for the study who are responsible for safeguarding the interests of all trial participants, assessing the safety and efficacy of the treatment during the trial, and for monitoring the overall conduct of the trial. The DMSC receives and reviews the accruing data from the trial and provides recommendations about stopping or continuing the trial. The DSMC may also formulate recommendations to enhance the trial’s scientific integrity and timeliness including recommendations relating to the selection/ recruitment/ retention of participants, their management, improving adherence to protocol-specified treatments, and procedures for data management and quality control. The DSMC operates under the guidance of an approved Charter.

Key responsibilities of the DSMC include but are not limited to:

• Reviewing and approving: the DSMC charter, the trial protocol, informed consent documents, methods for bias control, statistical analysis plan including methods for handling missing data and final analyses, data and safety monitoring plan including interim monitoring for safety efficacy, and futility, data table shells, study organizational and operational procedures, study timeline and milestone plan and assessing data quality, including completeness
• Monitoring recruitment and losses to follow-up
• Monitoring compliance with the treatment protocol by participants and investigators
• Evaluating study timeliness and progress toward meeting milestones, and recommending modifications as appropriate
• Monitoring evidence for treatment differences in the main efficacy outcomes
• Monitoring the safety of treatment (e.g. toxicity, adverse events)
• Deciding whether to recommend that the trial continues as planned or whether recruitment or treatment should be terminated in some treatment groups
• Reviewing proposed major modifications to the study prior to their implementation (e.g., increasing target sample size, dropping an arm based on other trial outcomes or toxicity results)
• Suggesting additional data analyses
• Assessing the relevance and impact of external evidence including published reports of related studies submitted by NEI, the study leadership, or DSMC members to determine whether the study needs to be changed or terminated
• Reviewing proposals for sub- or ancillary studies for scientific merit and potential impact on the trial
• Ensuring the timely and accurate reporting of main results from the trial
• Reviewing and approving the primary trial manuscript(s) with regard to determining that the results are fairly presented and the conclusions appropriate, prior to submission for publication(s) or presentation(s)

Dispute Resolution:

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

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. SBIR and STTR recipients may retain the rights to data generated during the performance of an SBIR or STTR award for up to 20 years after the award date, per the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Program Policy Directive. An acceptable Data Management and Sharing plan can reference and incorporate these data rights. Further information about SBIR and STTR data rights are enumerated in the NIH GPS.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

NIH requires that SBIR/STTR recipients submit the following reports within 120 days of the end of the grant budget period unless the recipient is under an extension.

• Final RPPR (requirements have recently changed - please see the NOT-OD-17-085)
• Final Invention Statement and Certification (HHS 568)
• Annual Invention Utilization Reports
• Federal Financial Report (FFR)
• SBIR.gov

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

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipientsof Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipientsof applicable NIH grants and cooperative agreementsare 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 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.Proceedingsinformation 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 2 CFR Part 200 – Award Term and Conditionfor Recipient Integrity and Performance Matters.

Disclosure of Foreign Relationships Reporting Requirements

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

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

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

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

Agency Recovery Authority and Repayment of Funds

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

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

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

Section VII. Agency Contacts

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

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

Paek Lee, PhD
National Eye Institute (NEI)
Telephone: 301-435-8164 
Email: paek.lee@nih.gov

Tony Gover, PhD
National Eye Institute (NEI)
Telephone: 301-529-7370 
Email: tony.gover@nih.gov

Brian Hoshaw, PhD
National Eye Institute (NEI)
Telephone: 301-402-0566
Email: brian.hoshaw@nih.gov

Karen Robinson Smith
National Eye Institute (NEI)
Telephone: 301-435-8178
Email: Karen.Robinson.Smith@nei.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.

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

The SBIR Program is mandated by the Small Business Innovation Development Act of 1982 (P.L. 97-219), reauthorizing legislation (P.L. 99-443) P.L. 102-564, P.L. 112-81 (SBIR/STTR Reauthorization Act of 2011), as reauthorized and extended under P.L. 114-328, Section 1834, P.L. 115-232, and P.L. 117-183. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.

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