Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title
Analytical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U44 Clinical Trial Optional)
Activity Code

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

Announcement Type

Reissue of PAR-18-549

Related Notices

    See Notices of Special Interest associated with this funding opportunity

  • January 22, 2024 - This PAR has been reissued as PAR-24-098.
  • August 9, 2023 - Notice of Early Termination of PAR-21-057. See NOT-NS-23-103.
  • June 12, 2023 - Implementation of the NIH SBIR and STTR Foreign Disclosure Pre-award and Post-Award Requirements. See NOT-OD-23-139. (See updates incorporated into NOFO content in Sections IV, V, VI, and VIII applicable for applications submitted for due dates on or after September 5, 2023.)
  • February 23, 2023 - Notice of Change to Minimum Performance Standards for SBIR and STTR Applicants. See Notice NOT-OD-23-092.
  • NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
  • NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
  • October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available. See Notice NOT-OD-22-018.
  • September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice NOT-OD-21-181.
  • August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022. See Notice NOT-OD-21-169
  • August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170
  • April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109
  • October 01, 2021 - Notice of Special Interest: Biomarker Discover and Validation in Functional Neurological Disorders. See Notice NOT-NS-22-010.
  • March 19, 2021 - Notice of Correction for PAR-21-057. See Notice NOT-NS-21-043.

Funding Opportunity Announcement (FOA) Number
PAR-21-057
Companion Funding Opportunity

PAR-21-056 - Analytical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 Clinical Trial Optional)

PAR-21-058 - Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 Clinical Trial Optional)

PAR-21-059 - Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U44 Clinical Trial Optional)

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.853

Funding Opportunity Purpose

The purpose of this Program Announcement (PAR) is to enable analytical validation of strong candidate biomarkers for neurological and neuromuscular disorders and conditions. Specifically, the goal of this PAR is to enable the rigorous validation of analytical methods for biomarker measurements, which should include evaluation of the detection method, its performance characteristics, and the optimal conditions that will generate reproducibility and accuracy consistent with FDA guidelines. This PAR assumes that 1) a candidate biomarker has already been identified, 2) detection method technology has already been developed, and 3) the research and/or clinical need and potential context of use has been identified.

Key Dates

Posted Date
November 19, 2020
Open Date (Earliest Submission Date)
January 22, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date.

Application Due Date(s)

February 22, 2021, June 22, 2021, February 22, 2022 June 22, 2022, February 22, 2023, June 22, 2023

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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

AIDS Application Due Date(s)

May 4, 2021, September 7, 2021, May 7, 2022, September 7, 2022, May 7, 2023 by 5:00 PM local time of applicant organization.

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

Scientific Merit Review

June 2021, October 2021, June 2022, October 2022, June 2023, October 2023

Advisory Council Review

October 2021, January 2022, October 2022, January 2023, October 2023, January 2024

Earliest Start Date

November 2021, February 2022, November 2022, February 2023, November 2023, February 2024

Expiration Date
New Date August 8, 2023 per issuance of NOT-NS-23-103. (Original Expiration Date: September 08, 2023 )
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

A biomarker is a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Biomarker modalities are diverse, and can include omics, imaging, behavioral, digital and physiologic endpoints, as well as composite biomarkers or biomarker signatures. Because the measurement of the biomarker is integral to defining the biomarker, it is necessary to describe the biomarker in terms of its biological source or matrix, measurable features, and the analytic method used to measure it.

Biomarkers are critical to the discovery and development of therapeutics and can serve a variety of functions such as verifying therapeutic target engagement, improving trial design by patient stratification, and facilitating clinical care decisions. Despite the active pace of discovery of novel biomarker candidates, few biomarkers progress beyond discovery to analytical validation and clinical practice, and robust, well-validated biomarkers for use in Phase II and Phase III clinical trials remain scant. Thus, there is a critical need to advance validation of biomarkers to improve public health, particularly for disorders of the nervous system where advancing therapeutics from discovery to the market is notoriously challenging.

This PAR is intended to address the gap in biomarker validation by encouraging rigorous analytical validation of the biomarker detection method. Analytical Validation is defined as the process of establishing that the performance characteristics of the measurement(s) are acceptable in terms of the sensitivity, specificity, accuracy, precision, and other relevant performance characteristics using a specified technical protocol (which may include sample collection and standardization procedures). The level of analytical rigor that is necessary depends upon the characteristics of the biomarker, the detection technology, and the intended category(ies) of biomarker (diagnostic, prognostic, predictive, pharmacodynamic/response, monitoring, safety, or susceptibility/risk) within the proposed context of use(s). Analytical validation establishes the measurement's technical performance so that final clinical validation can be established. Applicants with a detection method that has already been analytically validated for its intended Context of Use may apply directly to the companion PAR, Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 - Clinical Trial Optional) which addresses retrospective and/or prospective clinical validation of candidate biomarkers for use in clinical trials and/or clinical practice.

Research Objectives

Applications to this PAR must propose to conduct analytical validation of a biomarker or biomarker signature that already has a well-defined proof of concept and biological rationale. Premise and proof of concept must include evidence that the biomarker/biomarker signature has been tested in an appropriate clinical population, using either prospective or retrospective data or samples and shows sufficient sensitivity and specificity to warrant additional investment. In addition, applications to this PAR must include evidence that the detection method for the biomarker has been developed and subjected to initial evaluation of precision and analytical sensitivity. The application should clearly describe how the proposed study plans to optimize and standardize the detection method, as well as clearly define and rigorously test the analytic and pre-analytic variables to ensure broad and reliable clinical use across multiple sites.

This funding opportunity uses a cooperative agreement, milestone driven mechanism that enables significant input from NIH staff to assist investigators with preparing and evaluating their analytical validation strategy.

The Analytical Validation PARs and companion Clinical Validation PARs are designed to enable the production of a package of evidence needed for FDA Biomarker Qualification Submission, which is encouraged but not required as part of the application process. For more information on the Biomarker Qualification program see: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/BiomarkerQualificationProgram/default.htm

Entry Criteria

Entry Criteria should include the following:

  • Within NINDS mission: The project should focus on detection methods where the biomarker is likely to be used as a tool in the diagnosis, treatment, or prevention of diseases and conditions within the NINDS mission
  • Context of Use: The intended Context of Use (COU) should be identified and applications should include a statement with the heading Context of Use that fully and clearly describes the way the biomarker is expected to be used. Considerations involved in defining the context of use should include the biomarker category (susceptibility/risk, diagnostic, monitoring, prognostic, predictive, pharmacodynamic/response, or safety), biomarker modality, the method of detection and the clinical population characteristics. The COU is critical for determining the experimental design and level of analytical validation required, therefore it should be carefully considered and clearly defined. Context of use statements are discussed extensively in the Framework for Defining Evidentiary Criteria for Biomarker Qualification developed by the Biomarkers Consortium: https://fnih.org/sites/default/files/final/pdf/Evidentiary%20Criteria%20Framework%20Final%20Version%20Oct%2020%202016.pdf
  • Evidence of preliminary validation of the biomarker: Preliminary data illustrating that the biomarker reflects the intended pathophysiology and/or clinical endpoint appropriate for the Context of Use are required. Evidence should include a preliminary estimate of the clinical sensitivity and specificity and data illustrating the detection method has been developed and subjected to initial evaluation of precision and sensitivity at a minimum.

Application Characteristics:

  • A strong justification for use of the proposed detection method and biomarker including clinical and/or research unmet need should be included.
  • Feasibility, including potential added clinical burden and cost should also be directly addressed.
  • The status of the existing detection method and the plan for its optimization in clinical laboratories or point of care settings should be described.
  • The project should include analytical validation in multiple testing sites. If a single site is proposed, a scientific justification should be included.
  • Milestones describing the metrics for evaluating analytical validation to assess success in achieving each of the research plan’s objectives must be included.
  • The Biomarker or biomarker signature should be described using the FDA-NIH Biomarker Working Group BEST (Biomarkers, EndpointS, and other Tools) Resource, available from: https://www.ncbi.nlm.nih.gov/books/NBK326791/. Biomarker categories include:
    • monitoring biomarkers to track the success of a therapeutic intervention or disease progression
    • diagnostic biomarkers for detecting clinical manifestation of disease
    • prognostic biomarkers for predicting outcomes
    • predictive biomarkers for determining responders and non-responders to a therapeutic intervention
    • pharmacodynamic/response biomarkers for demonstrating therapeutic target engagement
    • safety biomarkers to indicate the likelihood, presence, or extent of an adverse effect, and
    • susceptibility/risk biomarkers that indicate the potential for developing a disease or medical condition in an individual who does not currently have a clinically apparent disease.

Although an individual indicator may be useful as more than one category of biomarker (i.e. both diagnostic and monitoring) the type of evidence required to validate it depends on the biomarker category specified; for example, a monitoring biomarker would need to demonstrate robustness in a longitudinal study design whereas a diagnostic may be evaluated with a cross sectional design. Thus, defining the biomarker category(ies) is essential to developing the experimental design and analytical performance necessary to validate it.

  • The research strategy should clearly describe how the application will utilize a rigorous design, execution, and interpretation of the proposed studies. NINDS encourages investigators, whenever possible, to address these elements directly in their applications.

Analytical Validation should include the following metrics with use of FDA guidance standards appropriate for the Context of Use

  • Accuracy
  • Precision
  • Analytical sensitivity
  • Analytical specificity including interfering substances or signals
  • Reportable range of test results for the test system
  • Reference intervals (normal values) with controls and calibrators
  • Harmonization of analytical performance of the detection method to be performed in multiple laboratories
  • Establishment of appropriate quality control and improvement procedures
  • Any other performance characteristics necessary for establishing calibration and control procedures

Responsiveness Criteria

Responsive studies include analytical validation of biomarker detection methods that indicate pharmacodynamic responses to therapeutics, predict efficacy or safety response as well as those for diagnostic, prognostic and disease progression or risk/susceptibility detection.

Applications Not Responsive to this FOA

Non-responsive studies include those seeking to develop therapeutic agents or devices as the primary intent, as well as those seeking to answer specific questions about clinical efficacy, effectiveness, and/or clinical management as the primary intent. Studies using animal models are non-responsive. Studies that fail to include milestones are also considered non-responsive. Non-responsive applications will be administratively withdrawn without review.

Collaborations

Multi-disciplinary collaboration among scientific investigators, developers, clinicians, statisticians, consultants, and clinical laboratory staff must be an integral part of the application. Projects proposed for this PAR should utilize multi-site design as applicable, with standardized data stewardship to ensure that data are reusable and accessible.

Investigators are encouraged to form collaborations with individuals knowledgeable in the FDA qualification process as well as those familiar with the process of analytical validation, including statistical design and analysis experts.

Leveraging Existing Resources

Applicants should leverage existing research resources for their studies. Such resources may include clinical biospecimen samples from the NINDS Human Biospecimen and Data Repository (BioSEND; https://biosend.org/) or other existing biospecimen, imaging and data repositories. Leveraging the research resources from advocacy groups, private research foundations, academic institutions, other government agencies and the NIH Intramural program are also encouraged. Studies are also encouraged to leverage the resources of ongoing clinical trials supported through other Federal or private funds.

Project Milestones

A project timeline with annual milestones must be included in the application (see Section IV). Milestones should describe project decision points with results-driven, quantitative metrics for go/no-go decision making throughout the funding period.

The NIH Program Official will contact the applicant to discuss the proposed milestones prior to the award. The Program Officer and Scientific Officer will discuss with the Program Director(s)/Principal Investigator(s) any recommended changes to the research plan or suggestions from peer review, and the plan will be revised as appropriate prior to the award.

Reproducibility and Data Sharing

To improve reproducibility and community uptake, investigators are expected to share code/scripts, analytic tools/statistical models, protocols/processes and metadata before the end of the project’s period of performance. The resource sharing plan should describe where information and data will be shared, including where the original controlled datasets exist and how to request access to them. Investigators should incorporate plans for sharing and dissemination of the data, protocols, and any analytical methods in their research sharing plan and project timeline. Budgets should reflect any costs associated with these efforts. Information on many available NIH supported or frequently used repositories is available at: https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html

Applicants collecting biofluid samples from prospectively enrolled study participants are encouraged to share samples through the NINDS biomarker repository, BioSEND (https://biosend.org/ ) to provide the broader scientific community with a data resource for hypothesis generation and test validation. Applicants should contact BioSEND to incorporate sharing plans and cost in their application.

Pre-Application Consultation

Under this Cooperative Agreement mechanism, NINDS Program Staff will have substantial communication and involvement with researchers in decision making prior to award and during the conduct of the study to provide oversight of data and safety monitoring, ensure the timely completion of the proposed studies and to maximize the positive impact of the studies on upcoming clinical trials.

Applicants are strongly encouraged to consult with NINDS Program Staff early on during the planning for an application. This early contact will provide an opportunity to discuss and clarify NINDS policies and guidelines, including the scope of the project relative to the NINDS mission and intent of this PAR. These discussions can also provide any needed clarification regarding development of an appropriate timeline and milestone plan.

Funding Considerations

Applications within the top scoring meritorious range will be considered for funding. Within that range, priority may be placed on applications that fill a critical program gap to ensure biomarker development that is reflective of the breadth of disorders and conditions within NINDS’s mission. Additionally, priority will be given to biomarkers that: 1) address an unmet medical need, 2) are supported by a strong biological rationale, 3) include a carefully designed plan for performance evaluation, 4) include a plan for standardization of samples and data collection for use in validation and 5) provide a strong justification for the utility of the biomarker in the clinical setting or the added value in a clinical research design.

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

Section II. Award Information

Funding Instrument

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

Application Types Allowed
Revision
New (Fast-Track)
Resubmission (all phases)

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

Clinical Trial?
Optional: Accepting applications that either propose or do not propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Budgets up to $700,000 total costs per year for Phase I and up to $1,500,000 total costs per year for Phase II may be requested.

Award Project Period

According to statutory guidelines, award periods normally may not exceed 6 months for Phase I and 2 years for Phase II. Applicants are encouraged to propose a project duration period that is reasonable and appropriate for completion of the research project.

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

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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

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

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

    1. SBIR and STTR. Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), an Indian tribe, ANC or NHO (or a wholly owned business entity of such tribe, ANC or NHO), or any combination of these; OR
    2. SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern, unless that single venture capital operating company, hedge fund, or private equity firm qualifies as a small business concern that is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States; OR
    3. SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with 121.705(b) concerning registration and proposal requirements.
  3. Has, including its affiliates, not more than 500 employees.

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

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

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

    Definitions:

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

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

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

Performance Benchmark Requirements

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

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

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

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

  • For companies that have received more than 15 Phase II awards from all agencies over the past 10 fiscal years (excluding the two most recently completed fiscal year): Companies that meet this criterion must show an average of at least $100,000 in revenues and/or investments per Phase II award or at least 0.15 (15%) patents per Phase II award resulting from these awards during the past 10- fiscal year period. Applicants that fail this benchmark will not be eligible to apply for New Phase I, Fast-track or Direct Phase II (if applicable) awards for a period of one year. This requirement does not apply to companies that have received 15 or fewer Phase II awards over the 10-fiscal year period, excluding the two most recently-completed fiscal years.
  • For application deadlines that fall on or after April 5, 2023: For companies that have received more than 50 Phase II awards from all agencies over the past 10-fiscal years (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $250,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period. Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 50 or fewer Phase II awards over the 10-fiscalyear period, excluding the two most recently-completed fiscal years.
  • For application deadlines that fall on or after April 5, 2023: For companies that have received more than 100 Phase II awards from all agencies over the past 10-fiscal years (excluding the two most recently completed Fiscal Year): Companies that meet this criterion must show an average of at least $450,000 of aggregated sales and investment per Phase II award over the past 10-fiscal year period. Applicants that fail this benchmark will not be eligible to receive more than 20 total Phase I and Phase II awards for a period of one year from the date on which such determination is made. This requirement does not apply to companies that have received 100 or fewer Phase II awards over the 10-fiscalyear period, excluding the two most recently-completed fiscal years.

Foreign Institutions

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

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

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

Required Registrations

Applicant Organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

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

Each PD/PI must commit a minimum of 10% effort to the project.

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

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

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

Contractual/Consortium Arrangements

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

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

We encourage you to contact a program officer listed in Section VII with questions about this because occasionally, deviations from these requirements may occur, and must be approved in writing by the funding agreement officer after consultation with the agency SBIR Program Manager/Coordinator. In Phase I and Phase II, at least 40% of the research or analytical effort must be performed by the small business concern and at least 30% of the research or analytical effort must be performed by the single, partnering research institution. The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct, F&A/indirect costs, and fee attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of the SF424 (R&R) application forms.

A small business concern may subcontract a portion of its SBIR or STTR award to a Federal laboratory within the limits above. A Federal laboratory, as defined in 15 U.S.C. 3703, means any laboratory, any federally funded research and development center, or any center established under 15 U.S.C. 3705 & 3707 that is owned, leased, or otherwise used by a Federal agency and funded by the Federal Government, whether operated by the Government or by a contractor.

The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or Phase II will be the total of the requested costs attributable to each party, unless otherwise described and justified in Consortium/Contractual Arrangements of the PHS 398 Research Plan component of SF424 (R&R) application forms.

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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:

Carol Taylor-Burds, PhD

National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: carol.taylor-burds@nih.gov

Page Limitations

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

Instructions for Application Submission

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Applications should include an Intellectual property (IP) strategy. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials.

Applicants should describe the IP landscape surrounding their biomarker and its measurement. Applicants should describe any known constraints that could impede biomarker development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar biomarkers that are under patent protection and/or on the market, etc.) and how these issues could be addressed with achieving the goals of this program. If the applicant proposes using an agent(s) whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should include a letter (see letter of support) from any entities owning the IP indicating there will not be any limitations imposed on the studies or the product which would impede achieving the goals of the funding program.

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

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

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

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

Other Attachments:

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

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

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

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

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

Other Plan(s):

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

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

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

This PAR supports the validation of analytical methods for biomarker measurements, including evaluation of the detection method, its performance characteristics, and the optimal conditions that will generate reproducibility and accuracy consistent with FDA guidelines that are fit for the purpose of the detection method.

Specific Aims

Briefly provide the Context of Use(s) for the biomarker, the biological research rationale for the identified biomarker, and a cogent argument outlining its importance and unmet need. Briefly describe the project aims, including the technical questions to be answered and the performance outcomes and characteristics needed in order to be used for the stated Context of Use(s). A scientific hypothesis is not required for this type of application.

Research Strategy

The Research Strategy Section should include the following sections

Rationale and Unmet Need

  • Define the disease or condition and the clinical population focus of the biomarker/biomarker signature.
  • Define the intended clinical Context of Use for the biomarker and its measurement. Include information on characteristics of the sample (i.e., specimen, image, EEG, behavioral endpoint, algorithm) to be used.
  • Describe the unmet need for the candidate biomarker and why the biomarker and its detection method will be feasible to conduct in the intended future clinical setting.
  • If applicable, provide a comparison to existing detection methods available for the biomarker and disease or condition of interest.
  • Describe the potential for the proposed studies to significantly advance translational medicine in the disease or condition area described.
  • Depending on the type of biomarker, address the probability for the biomarker and its detection method to be broadly adopted by the health care community for use in treatment or prevention.

Preliminary Data

Describe the evidence that the biomarker and detection method have met the required Entry Criteria (see Section I):

  • Describe the evidence that the biomarker has undergone initial testing in the relevant clinical population using retrospective or prospective data, including the initial sensitivity(ies) and specificity(ies) that has/have been found.
  • Describe what the detection method is, publications demonstrating its utility and feasibility, and cite any patents for prototypes (if applicable).
  • Provide any additional preliminary data supporting an argument that the biomarker is ready for analytical validation.
  • Describe the development status of the assay or method of detection and its potential use in a clinical setting.
  • Provide a clear outline of the method of detection, including the current key reagents, technologies and types of specimens or signals that will be used (e.g., fresh frozen or formalin-fixed tissue, serum or plasma, neuroimaging signals, behavioral or physiological measures, or composite biomarker signatures).
  • Discuss whether any of the analytical validation metrics listed in Section I above have been analyzed or completed; if so, provide the metrics,

Approach - address each of the items below

Describe the plans to perform analytical validation of the method of detection and its biomarker within its proposed Context of Use, including any plans for refinement of the Context of Use. The approach should include:

  • Plan to obtain appropriate samples (i.e., specimens, imaging data, physiology, or behavioral data) for further development and optimization of the assay or method of detection
  • Power analysis/justification for sample sizes
  • Plan to initiate and complete validation of the assay or method of detection
  • Plan to ensure appropriate standardization of samples and data that are used to validate the assay or method of detection
  • Plan to address pre-analytic variables of the assay, such as sample collection and preparation, interference, as well as relevant demographic variables such as race, gender, age etc. (See (iv) Analytical specificity below)
  • Plan for evaluation of (i) Accuracy, (ii) Precision, (iii) Analytical sensitivity, (iv) Analytical specificity including interfering substances/signals, (v) Reportable range of test results for the test system, (vi) Reference intervals (normal values) with controls and calibrators, (vii) Harmonization of analytical performance characteristics if the detection method is to be performed in multiple laboratories, (viii) Quality control and improvement procedures, (ix) Any other performance characteristic required for test performance with determination of calibration and control procedures
  • Plan to address a revised Context of Use based on results of the analytical validation, such as establishing an alternate threshold or cut-off.
  • If applicable, provide detailed plans for validation of algorithm(s) for multi-modal biomarkers.

If an application proposes to use only a single site for analytical validation, then a short paragraph with the heading justification for single site analytical validation must be included clearly explaining why a multisite setting is unnecessary or impossible, such as for rare diseases/conditions that can only be diagnosed or treated in a few specialized settings

Timeline and Proposed Milestones (required)

Milestones and timelines must be provided under a separate, specific heading at the end of the Research Strategy Section. Milestones should describe project decision points with quantitative metrics for go/no-go decision making throughout the funding period. Annual quantitative milestones are required to provide clear indicators of a project's continued progress or emergent difficulties. Milestones will be used to monitor project progress as part of the evaluation for continued funding by the Program Director(s)/Principal Investigator(s), Program Official and Project Scientists. A timeline for the anticipated attainment of each milestone must be included.

Quantitative milestones are dependent on the project but should include items such as:

  • Progress metrics (i.e. enrollment goals, sample and data collection goals, key experiments conducted)
  • Performance metrics (i.e. level of consistency across replicates, reaching target sensitivity and specificity thresholds, demonstration of standardization across sites, data quality standards)
  • If applicable, qualification metrics (letter of intent submission for FDA qualification and/or consultations)
  • For each milestone, provide a brief description of the success criteria along with a brief justification for those criteria.
  • Provide a timeline for the anticipated attainment of each milestone.

Team Management Plan:

  • Applicants are strongly encouraged to form multidisciplinary teams that consist of clinical scientists, clinicians with drug development experience, regulatory experts, statisticians, and other academic/industry experts relevant to the therapeutic modality. Describe the team's ability to design the details of the plans and experiments, and to execute the research strategy.
  • Describe how the team will work together (e.g., data generation, reporting of data and integrated review across teams with various disciplines, decision-making, etc.) over the course of the project (and include letters of support below). This description should include an outline of roles and responsibilities for each team member

Letters of Support:

  • Applicants should include letters of support from consultants, contractors, and collaborators.
  • Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, consultants, and / or BioSEND if biospecimens are being collected.
  • If applying from an academic institution, include a letter of support from the technology transfer official who will be managing intellectual property associated with this project.
  • If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
  • If collaborating with a private entity, include a letter of support that addresses any agreement to provide agent(s), any limits on the studies that can be performed with said agent(s), any limitations on sharing of data (including negative results), and whether a licensing agreement(s) will be needed and in place once the project is funded. This letter should come from a high official within the private entity who has authority to speak on these issues.
  • If an application plans to utilize the infrastructure or resources of existing projects, whether funded by the NINDS, other governmental or non-governmental entities, letters of support detailing the terms of collaboration and data sharing must be included.
  • If existing biospecimens are to be used, include letters of support or approval for use of those samples, including those banked at BioSEND. For example, if samples include those adjudicated by the Parkinson's Disease Biospecimen Review Access Committee (PD-BRAC), a letter indicating BRAC approval should be included (https://pdbp.ninds.nih.gov/pd-brac).

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

All applications, regardless of the amount of direct costs requested for any given year, should include a Data Sharing Plan. If patent protection is being sought, investigators should explain how data will be shared after filing for patent protection to allow for both further research and the development of commercial products to advance forward, consistent with achieving the goals of the program.

  • Plans should describe how, where, and when the data, analytical code/scripts, metadata and protocols/standard operating procedures will be shared.
  • Applicants planning to collect biofluid samples from prospectively enrolled study participants should also provide the broader scientific community with a data resource for hypothesis generation, test validation, and discovery related through the NINDS biomarker repository, BioSEND (https://biosend.org/). Applicants should contact BioSEND to incorporate sharing plans and cost in their application. Note that costs for collection are NOT included as a component of the NINDS Biomarkers Repository award.

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.

The Appendix should include the following, as appropriate for the proposed study:

  • Standardized protocols for measuring the biomarkers proposed
  • For proposed ancillary studies, provide the protocol for the parent clinical trial or longitudinal study and the consent form for the parent study
  • For clinical trials, provide the consent forms to be used
  • If applicable, guidance documents provided by the FDA regarding qualification of the proposed biomarker(s)
PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Section V. Application Review Information

1. Criteria

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

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

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

Overall Impact

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

Scored Review Criteria

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

Significance

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

Further criteria specific to this opportunity:

  • Does the candidate biomarker address an unmet medical and clinical need?
  • Is there a strong biological and clinical rationale for the biomarker?
  • Will the proposed studies significantly advance translational medicine in the disease or condition area described?
  • Are the biomarker and its detection method likely to be broadly adopted by the health care and/or research community for use in treatment or prevention decisions or studies?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed?

Investigator(s)

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

Further criteria specific to this opportunity:

  • Are the investigators knowledgeable and experienced about the biological target and/or disease biology?
  • Do the investigators have sufficient expertise in the areas of development and analytical validation of the assay within the specified clinical context of use, statistical analysis, experimental design as appropriate for the project?
  • Will the team be able to manage the further development of the detection method should the detection method be successful so that it is distributed and ultimately available to the healthcare and/or research community?
  • Are the roles of each collaborator carefully defined in the research plan?

In addition, for applications involving clinical trials

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

Innovation

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

Further criteria specific to this opportunity:

  • Is there innovation in the detection method, study design or clinical context? Does the detection method offer a significant improvement over existing methods of detection for the proposed type of biomarker?

In addition, for applications involving clinical trials:

  • Does the design/research plan include innovative elements, as appropriate, that enhance the biomarker’s sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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

Further criteria specific to this opportunity:

  • Are the outcomes and performance criteria clearly stated and scientifically justified?
  • Are pre-analytic variables adequately addressed and are there plans to include control of these variables?
  • Are the plans for optimization and validation appropriate for the biomarker detection method being used?
  • Is there an adequate plan to ensure that samples and data are collected in a standardized and representative way?
  • Are there plans to ensure that the study is scientifically rigorous with appropriate use of blinding, randomization, replicates, and controls in place to minimize bias?
  • Is the statistical analysis plan clearly described and appropriate for the experimental design with adequate statistical power to test the performance of the detection method?
  • If a single site design is proposed, is it scientifically justifiable and sufficiently representative to meet the goals of the study?

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

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

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

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

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

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

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

Data Management and Statistical Analysis

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial? If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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

Milestones and Timeline

Do the milestones describe appropriate project decision points with quantitative metrics for go/no-go decision making throughout the funding period? Do the annual quantitative milestones provide clear indicators of the project's continued progress? Is the timeline appropriate for the anticipated attainment of each milestone? Are the progress metrics (i.e. enrollment goals, sample and data collection goals, key experiments conducted) appropriate for the project's successful and timely completion? Are the performance metrics (i.e. level of consistency across replicates, reaching target sensitivity and specificity thresholds, demonstration of standardization across sites, data quality standards, etc) satisfactory for the context of use proposed? If applicable for the application, is the timeline for the qualification metrics (letter of intent submission for FDA qualification and/or consultations) appropriate? Are the quantitative success criteria for each milestone clear, appropriate and sufficiently justified?

Study Timeline

Specific to applications involving clinical trials

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

Phase II Applications

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

Not Applicable

Phase I/Phase II Fast-Track Applications

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

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

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Phase IIB Competing Renewals

Not Applicable

Revisions

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

Additional Review Considerations

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

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

Intellectual Property

1) Does the application outline any known constraints that could impede biomarker development (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar biomarkers that are under patent protection and/or on the market, etc.) and how these issues could be addressed while achieving the goals of this program? 2) Does the applicant outline the IP landscape of their biomarker assay or method of detection? 3) If applicable, how strong is the applicant's IP portfolio/position (pertinent to the proposed project), and to what extent does the applicant have a reasonable strategy to protect its IP going forward? 4) If the applicant has filed patents pertinent to the biomarker detection method, do they provide details about those patents? 5) If IP will be shared among co-investigators, does the applicant provide details about the plans for IP sharing?

Select Agent Research

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

Resource Sharing Plans

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

Reviewers should include specific comments on whether the Resource and Data Sharing plan includes adequate information on the following questions:

  • Is the plan for sharing the protocols, related tools, software and/or code used for evaluating the biomarker appropriate? Are the repositories specified and appropriate?
  • Will the final curated datasets be made available? If not, is there a justifiable reason? If so, is there a clear description of where the data will be held and how to request access?
  • Is the timeline for disseminating information appropriate?

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

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

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

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

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

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

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

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

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

A finding of foreign involvement with countries of concern will not necessarily disqualify an applicant. NIH (and CDC or FDA, as applicable) will provide SBC applicants the opportunity to address any identified security risks prior to award. Final award determinations will be based on 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.

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 above, and the risk cannot be resolved.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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: Grantee 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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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

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

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

Report fraud, waste and abuse

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

  • Defining the overall research objectives and approaches, and for planning, conducting, analyzing, interpreting, drawing conclusions on their studies, publishing and sharing the results.
  • Determining experimental approaches, designing protocols, and overseeing the conduct of experiments.
  • Developing and proposing rigorous milestones that will be achieved during the project period;
  • Overseeing and coordinating the effort of the multi-disciplinary team and participating institutions and ensuring their optimal integration.
  • Overseeing the conduct of research projects and ensuring their scientific rigor, including assumptions for the design of the experiments, the results of the investigations, interpretations of the results, and for concluding whether milestones have been met or not. In cases when NINDS Program staff request raw data, awardees agree to provide the data.
  • Ensuring compliance with the applicable mandatory regulations (including protection of human subjects).
  • Adhering to the NIH policies regarding intellectual property, data release, and other policies that might be established during the course of this activity.
  • Submitting updates on progress and problems in a brief format as agreed upon with the NIH;
  • Submitting annual updates on human subject and accrual reports upon initiation of validation studies when appropriate.
  • Participating in progress meetings (teleconferences) that are organized by NIH staff once or twice a year.
  • Inviting NIH Program Staff to participate in interactions with regulatory agencies, include providing meeting dates and agenda.
  • Provide study reports from CROs, meeting minutes (and associated data packages if applicable), letters and other forms of communications with FDA, and other authorities, and to provide IND# and registration numbers in ClinicalTrial.gov, if applicable.
  • Awardees will retain custody of and have primary rights to the data, technologies, and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards (as appropriate regarding clinical trials):

  • Each project will have the support of one or more Project Scientists from NIH Program staff who are assigned an administrative role for the neurological or neuromuscular disorder being studied and have expertise in the implementation of the NINDS Biomarker Program in Translational Research.
  • The Project Scientists will have substantial scientific/programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants.
  • Providing input on the milestones and makes decisions regarding their finalization.
  • Providing input on experimental and clinical approaches, assisting in designing protocols, and consulting on updates to project milestones;.
  • Assessing the progress of the project towards the specified milestones, and for recommending if further funds should be released to the project.
  • In consultation with the PDs/PIs, may add critical experiments that need to be conducted prior to or during the award as an additional milestone(s). In most cases, these studies will be supported by additional funds.
  • Participates in meetings together with PDs/PIs with regulatory agencies related to the funded project when appropriate.
  • Providing advice to the awardees on specific scientific, analytical, and clinical issues as appropriate.
  • Assisting and advising awardees with regard to various regulatory and compliance issues as appropriate.
  • Participating in quarterly or biannual teleconferences with PDs/PIs to monitor progress and facilitate cooperation as appropriate.
  • Tracking monthly accrual of participants for clinical testing to ensure proper completion of this essential step as appropriate.
  • Contributing to publications and presentations resulting from the project if appropriate.
  • An important part of the NINDS Biomarker program is the coordination of research efforts across different funding mechanisms and research capabilities, and the coordination among efforts aimed at different neurological and neuromuscular disorders. NINDS Project Scientists will have the primary responsibility for this overall coordination.
  • Additionally, an NINDS Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Some Program Officials may also have substantial programmatic involvement (as Project Scientists/Coordinators). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NINDS waiver as stated above.
  • NIH leadership will make decisions on project continuation based on Program staff recommendations, programmatic prioritizations and budget considerations. NINDS Program staff may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous year. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, NINDS portfolio balance and program priorities, competitive landscape, and availability of funds.

Areas of Joint Responsibility include:

  • Clarifying, negotiating and finalizing the milestones and timelines.

Dispute Resolution:

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

Data Management and Sharing

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

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

3. Reporting

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

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

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

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

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

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. In addition, regular updates are required at the time of all SBIR/STTR annual, interim, and final Research Performance Progress Reports (RPPRs).

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 withhold funding until the covered relationship has been dissolved. The recipient will be required to submit documentation verifying the relationship has been terminated. If the risk cannot be resolved, 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.

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

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

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

Scientific/Research Contact(s)

Carol Taylor-Burds, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: carol.taylor-burds@nih.gov

Mary Ann Pelleymounter, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email:mary.pelleymounter@nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: nindsreview@nih.gov

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

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

Authority and Regulations

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

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

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


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