Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Funding Opportunity Title
Investigational New Drug (IND)-enabling and Early-Stage Development of Medications to Treat Alcohol Use disorder and Alcohol-Associated Organ Damage (U43/U44 Clinical Trial Optional)
Activity Code

U43 Small Business Innovation Research (SBIR) Cooperative Agreement Phase I

U44 Small Business Innovation Research (SBIR) Cooperative Agreement – Phase II, Fast-Track

Announcement Type
Reissue of PAR-18-578
Related Notices
None
Funding Opportunity Announcement (FOA) Number
PAR-22-102
Companion Funding Opportunity
PAR-22-103, UT1/UT2 Small Business Technology Transfer (STTR) Cooperative Agreement – Phase I/Small Business Technology Transfer (STTR) – Cooperative Agreements - Phase II
Assistance Listing Number
93.273
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) supports Small Business Innovation Research (SBIR) applications from small business concerns (SBCs) that propose the development of therapeutic agents for the treatment of alcohol use disorder (AUD) and/or alcohol associated organ damage (AAOD). As a starting point, eligible applicants must identify a therapeutic candidate with a robust body of background data in the basic science and early discovery phases to be ready for transition to the preclinical and clinical phases of development. Data may include having sufficient bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and/or target engagement, and other favorable properties that are consistent with the desired clinical application. Projects responsive to this announcement could be undertaken at any point along the drug development continuum, from late discovery (i.e., lead optimization/early safety) up to early-stage clinical trials. For small molecules, the earliest stage of eligibility for this Award is already having small-molecule compounds with proof of desired pharmacological activity. For biologics, the profiling of promising product candidates in animal models of AUD or AAOD will be allowed as the earliest entry point. The ultimate purpose and goal of this FOA is to advance molecules closer to U.S. Food and Drug Administration (FDA) approval. Milestones will be commensurate with the project proposed and the purpose of this FOA. This FOA supports early-phase clinical trials, although these are not required.

Women-owned and socially or economically disadvantaged small business are encouraged to apply.

Key Dates

Posted Date
January 21, 2022
Open Date (Earliest Submission Date)
February 28, 2022
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
March 28, 2022 March 28, 2022 Not Applicable July 2022 August 2022 January 2023
December 05, 2022 December 05, 2022 Not Applicable March 2023 May 2023 July 2023
March 27, 2023 March 27, 2023 Not Applicable July 2023 August 2023 December 2023
December 04, 2023 December 04, 2023 Not Applicable March 2024 May 2024 July 2024
March 27, 2024 March 27, 2024 Not Applicable July 2024 August 2024 December 2024
December 04, 2024 December 04, 2024 Not Applicable March 2025 May 2025 July 2025

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

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

Expiration Date
December 05, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the SBIR/STTR (G) Instructions inthe 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.

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Currently, there are only three medications (four formulations) approved by the FDA for the treatment of alcohol use disorder (AUD). The need for additional medications to treat those affected by AUD is urgently needed.In addition,alcohol misuseaffects virtually all tissues and is linked with dysfunction and failure of many organs and systems including the liver, heart, pancreas, lung, bone, and skeletal muscle, as well as digestive, vascular, endocrine, and immune systems.There are currently no FDA-approved therapies for alcohol-associated organ damage (AAOD) so effectivetherapies to prevent and treat AAOD are urgently needed.

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to provide support to SBC for the optimization, development, and translation of pharmaceutical research discoveries into new treatments for disorders that fall under the mission of NIAAA.The goal is to advance small molecules, natural products or biologics for AUD and AAOD through the drug development pipeline towards FDA approval and ultimately, commercialization.

Due to the urgency of this public health need, projects supporting a lead compound with a robust body of background data in the basic science and early discovery phases to be poised for transition to the preclinical and clinical phases of medications development will be prioritized. Background data may include rigorous preclinical testing, sufficient bioactivity, stability, manufacturability, bioavailability, and in vivo efficacy and/or target engagement. Applications focusing solely on basic science research such as: novel target identification/validation, generation of new animal models, development/testing of new human laboratory models, assay development, new biomarkers, or mechanistic studies of the neurobiology of AUD are not considered responsive. By the end of the funding period, projects are expected to achieve milestones that significantly move the compound towards the next phase of drug development (e.g., pre-IND meeting, Investigational New Drug (IND) application).

Women-owned and socially or economically disadvantaged small business are encouraged to apply.

Research Objectives

This FOA seeks applications that propose to advance the following classes of therapeutics beyond pre-clinical development by preparing to seek regulatory approval for future trials: small molecules, natural products, and biologics, which broadly include peptides, proteins, oligonucleotides, gene therapies, and cell therapies. Applicants are strongly encouraged to contact NIAAA Scientific/Research staff regarding the agent under development, to determine the fit for the FOA prior to submission

Examples of responsive drug development activities and corresponding SBIR Phase assignment includes but is not limited to,

Pre-clinical development – SBIR Phase I (Proof of Concept Phase)

  • Chemistry, Manufacturing, and Control (CMC) activities (e.g., master and working banks development, purification development, CMC analytical development, formulation development, scale-up manufacturing or cGMP manufacturing) for IND-enabling pharmacology/toxicology tests
  • Pharmacokinetic evaluations in species relevant for toxicology or human dose-prediction
  • Preliminary safety such as safety pharmacology and/or dose-range finding toxicology
  • Optimizing and/or validation of appropriate assays for pharmacokinetics, bioactivity (potency), target engagement markers or other assays to monitor safety to be used in human trials
  • Drug interaction studies between medication and alcohol
  • Further evaluation of compound safety/efficacy in established animal models,
  • IND-enabling studies

Pre-clinical development – SBIR Phase II (Research and Development)

The Phase II can support more extensive IND-enabling development activities.

  • IND-enabling toxicology, with toxicokinetics, if applicable
  • Tumorigenicity evaluations particularly for gene therapies and cell therapies, if applicable
  • Immunogenicity evaluations, if applicable
  • Biodistribution studies, if applicable
  • Large animal study to assess biocompatibility of means of clinical delivery of the candidate, if applicable
  • Validation of appropriate assays such as for target engagement markers to enable human use
  • IND and other regulatory submissions

Clinical development – SBIR Phase I

  • Evaluation of pharmacokinetics, preliminary safety, tolerability, alcohol interaction, dose-ranging, and/or initial efficacy in human subjects.

Clinical development - SBIR Phase II

For more advanced projects, a small early phase clinical trial can also be supported when feasible during the Phase II. Applications seeking to supportonlyearly-stage clinical trials with preliminary POC efficacy and safety data supported outside the SBIR/STTR program, may apply for a Direct to Phase II under this FOA.

Small, early-phase clinical trials that are appropriate include:

  • Proof-of-Concept
  • Pilot studies
  • Safety and Efficacy testing in a larger sample of human subjects

Milestones

Because therapy development is an inherently high-risk process, it is anticipated that there may be significant attrition as projects move through the therapy development process. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision-making for the project, and should have quantitative criteria associated with them (see Section IV.2 for details).

NIAAA intends to only move forward agents that are both efficacious and safe. Although the primary goals are to assess safety and toxicology, lack of evidence of a trend towards efficacy in the dose range where the candidate is safe can also be a consideration for discontinuation.

U44 Phase I/II transition

Applicants can submit separate Phase I (U43) or Phase II (U44) applications. However, if Phase I and Phase II are submitted together in one application (U44 Fast-Track), then an administrative review will be conducted by NIAAA Program staff to decide whether a project will be considered for transition from the Phase I to the Phase II. Phase II eligible projects must have a candidate that has been manufactured with satisfactory purity and stability, verified to have activity in vivo and/or in vitro as necessary, have bioavailability with a proper formulation, and have a good preliminary safety profile.

Prior to commencement of the clinical trial (defined as first subject signature on an informed consent form), the applicant must provide the following to NIAAA for review and/or approval.

  • Investigational Review Board (IRB) approval;
  • IRB approved Study protocol and Informed Consent;
  • FDA IND or IND waiver;
  • New or revised/updated data and safety monitoring plan;
  • Data and Safety Monitoring Board configuration and charter;
  • Agreement with NIAAA staff on updated timeline, milestones and budget for clinical trial
  • NIAAA approval of protocol and safety monitoring plan

Quality and Compliance Requirements

Since the goal of this program is to generate therapeutics which will be eligible for FDA approval, adherence to compliance and quality criteria is required.

  • It is expected that all IND-enabling nonclinical studies will be performed in a manner consistent with Good Laboratory Practices (GLP).
  • Investigational products should be produced under current Good Manufacturing Practices (cGMP). Bioassays such as pharmacokinetics, pharmacodynamics or immunogenicity should, when possible, be performed under GLP guidelines.
  • All clinical trials must be performed following Good Clinical Practices (GCP) and be in accord with NIAAA Policy.

Intellectual Property (IP)

Since the ultimate goal of the SBIR/STTR program is to bring new therapies to the market/patients, the program strongly encourages the awardees and/or their collaborators to obtain and retain any IP developed around the therapy during the project period (see instructions on attachment of letters to address IP issues in Section IV.2). Awardees are encouraged to identify and foster relationships with potential licensing and commercialization partners early in the therapy development process. PDs/PIs are expected to work closely with their institutional technology transfer officials to ensure that royalty agreements, patent filings, and all other necessary IP arrangements are completed in a timely manner and that commercialization plans are developed and updated over the course of the project. For rare or ultra-rare diseases where commercialization may be challenging, applicants are encouraged to discuss alternative strategies with NIAAA Scientific/Research staff to get further guidance.

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

  • Animal model development, basic research and studies of disease mechanisms, assay development
  • Early research such as identifying and validating targets and generation of preliminary agents that are not suitable for human testing
  • Development of risk, detection, diagnostic, prognostic, efficacy prediction biomarkers. (NIAAA recognizes that target engagement markers developed under the Phase I may evolve into predictive markers for treatment trials, but it is not the intent of this FOA to develop predictive biomarkers.)
  • Activities already performed utilizing other private or public funds to advance the agent
  • HIV/AIDS related research studies

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

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Renewal - Phase II
Resubmission - all Phases
Revision

 

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

Phase IIB budgets must be submitted in accordance with participating IC-specific budget limitations described in the current SBIR/STTR Program Descriptions and Research Topics of the NIH, CDC and FDA.

Award Project Period

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

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

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

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

    Definitions:

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

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

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

Phase I to Phase II Transition Rate Benchmark

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

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

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

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

Phase II to Commercialization Benchmark

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

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

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

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

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

Foreign Institutions

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

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

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

Required Registrations

Applicant Organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

 

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

3. Additional Information on Eligibility

Number of Applications

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review.

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

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).

Deviations from these requirements may be considered on a case by case basis. Please contact a program officer for additional information. Deviations must be approved in writing by the Grants Management Officer (GMO) after consultation with the agency SBIR Program Manager/Coordinator.

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this 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:

Dr. Abraham Bautista
Telephone: 301-443-9737
email: bautista@nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments:

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

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

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

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

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims:The Specific Aims section should include separate Aims delineated for each of the phases. A scientific hypothesis is not required.

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

A. Significance: Clinical Impact and Feasibility
B. Supporting Data for Entry
C. Detailed Plans for Approach (Including Milestones and Timelines)
D. Intellectual Property (IP) Strategy

A. Significance

Clinical Impact and Feasibility: Each application should focus on only one disorder or disease, even if the therapeutics proposed for development show activity in models for more than one disorder. This is because the target patient population and intended use guide the design of the therapy and the path for an IND, and the preclinical IND-enabling studies. Levels of tolerated toxicities may also differ between different disorders especially if the proposed treatment is chronic versus acute.

Describe the current state of knowledge of the etiology, clinical characteristics, and prevalence of the proposed disease indication.

Briefly discuss available treatments (if any), their limitations, and how the proposed project would provide an advantage over all existing therapies, regardless of therapeutic class (i.e., discussion only on within class comparisons is not sufficient).

If the therapy is an improvement over an earlier generation agent(s) that has not been marketed, discuss what advantages the new agent has. Include results from previous clinical trials with related agents.

*For Fast-Track and Phase II applications only - provide a Target Product Profile (TPP) table that shows the ultimate goals of the proposed therapy development effort, such as disease indication and stage, patient population, delivery mode and dosing regimen, treatment duration, and standards for clinical efficacy. Explain the rationale behind the minimally acceptable and ideal parameters for the clinical population.

B. Supporting Background Data

The Supporting Background Data contains, but is not limited to, sufficient bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and/or target engagement, and other favorable properties that are consistent with the desired clinical application.

Explain the choice of models or assays, primary, secondary and exploratory endpoints, and how they are clinically relevant. If multiple models have been employed, outline the pros and cons of each model and why one model may be more robust than another. Explain which model(s) is the one most frequently employed in IND-enabling studies to seek approval from the FDA.

Describe the procedures of how blinding and randomization were conducted, and whether independent replication was employed in these studies.

Describe bioavailability; include data and analyses performed to demonstrate the candidate can penetrate the blood-brain-barrier, if required for efficacy.

When interpreting the results, consider alternative interpretations of the experimental data, relevant literature in support of or in disagreement with the results, and include discussion of effect size in relation to potential clinical impact.

Applicants should explain what key data, if any, has been reproduced, by the applicants or by independent investigators.

(3) Discuss feasibility of production and reproducibility of production of the candidate.

C. Detailed Plans for Approach (Including Milestones and Timelines)

In this section applicants should elaborate on their research plans.Describe milestones to be used for measuring success in achieving each of the research plan's objectives. If applying for a Fast-Track, please delineate the milestones by Phase. One or more milestone should be used for each objective. For each milestone provide details on methods, assumptions, experimental designs, and data analysis plans (if the results are quantitatively measured). Specify the quantitative criteria for measuring success and the rationale for the quantitative criteria. Quantitative criteria should be robust and be consistent with the state-of-the-art in the field. Most of the time the quantitative criteria for success in the milestones will also be used for making go/no-go decisions and this should be specified. Specify the timeline for each milestone. There should be at least one milestone proposed for completion at the end of each year.

For applications proposing clinical trials, this information should not overlap with the Study Timeline submitted for the clinical trial.

Be sure to describe experimental designs, delineated for Phase I and/or Phase II. If the studies proposed are planned to be done in a Contract Research Organization (CRO), Contract Manufacturing Organizations (CMO), list the name(s) of the CRO(s) for the activities.

D. Intellectual property (IP) Strategy

Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

Applicants should describe the IP landscape surrounding their therapy. Applicants should describe any known constraints that could impede the development of their therapy (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed. 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 address any questions of freedom to operate consistent with achieving the goals of the program. Applicants should include a letter (see Letters of Support) from the entity who owns the IP indicating whether they will provide the agent(s), if there are any limitations on the studies that can be performed with that agent(s), agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.

If patents pertinent to the therapy 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 United States Patent and Trademark Office (USPTO) database links, if applicable.

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

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

-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) is in place. This letter should come from a high official within the private entity who has authority to speak on these issues.

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:

Appendix:

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

PHS Human Subjects and Clinical Trials Information

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 form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NIAAA Referral Office by email at bautista@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

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

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?)

Specific to this FOA:

Was the current state of knowledge of the etiology, clinical characteristics, and prevalence of the proposed disease indication adequately described?

Are available treatments (if any), their limitations, and how the proposed project would provide an advantage over all existing therapies been adequately described?

If the proposed therapy is an improvement over an earlier generation unmarketed agent(s), has the potential advantages of the new agent been described? Have results from previous clinical trials with related agents been included?

For Fast-Track and Phase II or Phase IIb applications only - Was a Target Product Profile table included and was the rationale behind the minimally acceptable and ideal parameters for the indication/clinical population explained?

In addition, for applications involving clinical trials

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

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?

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?

In addition, for applications involving clinical trials

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

Approach

Are the 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?

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?

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

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)?

Intellectual Property

Is the Intellectual Development Strategy described in detail including current patents, patent filings and future plans for IP filings? Are there any known constraints that could impede the development of the compound (e.g., certain restrictions under transfer or sharing agreements, applicant' previous or present IP filings and publications, similar therapies that are under patent protection and/or on the market, etc.) and how these issues could be addressed?

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?

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

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

Applications with Foreign Components

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

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process 

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

As part of the scientific peer review, all applications will receive a written critique.

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

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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).

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. 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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/.

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 athttp://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).

Milestones: Future support of a study funded under this FOA is contingent upon adequate completion of milestones.

2. Administrative and National Policy Requirements

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

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

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

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

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Report fraud, waste and abuse

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

Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the 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 recipients  for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

  • All aspects of their study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. The recipient agrees to accept close coordination, cooperation, and participation of NIAAA staff in those aspects of scientific and technical management of the study as stated in these terms and conditions.
  • Meeting NIAAA policy requiring that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study.
  • Upon implementation of the protocol, ensuring that each site, whether a single institution or a consortium of institutions, will follow the procedures required by the protocol regarding study conduct and monitoring, data collection, and quality control.
  • Support or other involvement of industry or any other third party in the study--e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIAAA support; or special access to project results, data, findings, or resources--may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIAAA.
  • Recipients are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NIAAA/NIH.
  • Obtaining prior written approval of the NIAAA Grants Management Specialist in consultation with the NIAAA Program Officer for any change in any of the key personnel identified in the Notice of Grant Award.

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

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

The NIH Project Scientist will be extramural staff from NIAAA, who will have substantial involvement above and beyond the normal program stewardship of the award. The NIH Project Scientist is a partner within the research team representing the government's interest in the substantive work of the research team with the following responsibilities:

  • Have substantial scientific/programmatic involvement during conduct of this cooperative agreement, through technical assistance, advice,
  • Coordinate with the recipients in monitoring issues relating to: design of the activities, recruitment, adherence to protocols, adjustment of study protocols, and management and technical performance.
  • Participate in all Steering Committee activities, including conference calls, subcommittees and special committees.
  • Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAAA staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, recipients will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.
  • Provide guidance and support in the development, assembly, and submission of all required regulatory documents, e.g., those regarding the use of investigational drugs, to the Food and Drug Administration.
  • Will not be involved in funding decisions and will not be allowed to attend review meetings of conflicted applications.

The NIH Program Official will be an NIAAA Staff who will be responsible for the normal scientific and programmatic stewardship of the award. Additional responsibilities include:

  • Participate in all Steering Committee meetings and conference calls.
  • Monitor recruitment status of the trial on an ongoing basis.
  • Monitor performance through consideration of quarterly meetings of the Steering Committee and annual reports, site visits, and compliance with NIH procedures.
  • Approve modifications to the research plan and/or study protocol(s) based on emerging data and/or other issues that impact progress of the project.
  • Determine if the recipient has met/achieved milestones throughout the project.
  • Determine if the recipient has met the milestones and feasibility requirements for transition of the project to the next year or stage of funding.
  • Reserve the right to obtain periodic external peer review, and recommend reviewers for, an assessment of progress and achievement of milestones.
  • Ensure timely registration of Phase I and Phase II trials in ClinicalTrials.gov.
  • Reserve the right to terminate or curtail the study (or an individual award) in the event of (a) failure to implement the study protocol, (b) a substantial shortfall in milestone achievement (e.g., participant recruitment, follow-up, data reporting and dissemination, quality control, or other major breach of the protocol), (c) substantive changes in the agreed-upon protocol with which NIAAA does not concur, (d) reaching a major study objective substantially before schedule with persuasive statistical evidence, or (e) human subject ethical issues that may dictate a premature termination.
  • Oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team.
  • Will be involved in funding decisions and attend review meetings of applications submitted in response to this FOA.

The NIAAA Staff shall not have dual roles as Project Scientist and Program Official

Dispute Resolution:

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

3. Reporting

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

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

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

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

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

Scientific/Research Contact(s)

For questions related to treatment of AUD:

Jenica Patterson, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-827-6166
Email: jenica.patterson@nih.gov
 

For questions related to the treatment of AAOD:

Svetlana Radaeva, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-1189
Email: sradaeva@mail.nih.gov

Peer Review Contact(s)

RV Srinivas, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone:301-451-2067
Email: srinivar@mail.nih.gov

Financial/Grants Management Contact(s)

Jeffrey Thurston
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-9801
Email: jeffrey.thurston@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, and P.L. 115-232. The basic design of the NIH SBIR Program is in accordance with the Small Business Administration (SBA) SBIR Policy Directive.

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