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

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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) supports applications from Small Business Concerns (SBCs) for exploratory clinical trials that contribute to the justification for a future trial to establish definitive efficacy (such as a Phase 3 clinical trial or a pivotal device trial). This includes Phase 1 and 2 clinical studies of drugs, biologics and biotechnology products, feasibility studies of devices, as well as preliminary clinical studies of surgical, behavioral or rehabilitation therapies. A wide range of trials at different stages of development are allowed, including first-in-human (as defined by the Food and Drug Administration), Phase 1 and 2 single-site clinical studies, and Phase 2b multicenter clinical studies. Applications should aim to generate data that inform further clinical development of the proposed intervention. The earliest studies should be designed to provide important initial information regarding the intervention (e.g., safety, tolerability, dosing, usability, acceptability). Later-stage studies will generally include randomization and blinding and should yield data that allow a clear go/no-go decision regarding whether the intervention should proceed to a definitive efficacy trial. This FOA is not intended to support the conduct of a clinical trial where the primary aim is to establish or confirm definitive efficacy (pivotal trials).

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will allow SBIR clinical trial applications through this FOA and will no longer accept clinical trial applications to prior small business announcements (see NOT-DK-16-030).

The mission of the NIDDK is to conduct and support medical research and research training and to disseminate science-based information on diabetes and other endocrine and metabolic diseases; gastrointestinal and liver diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases, to improve people’s health and quality of life. Traditionally, large pharmaceutical and biotechnology companies, as well as venture capital firms, have provided the resources needed to conduct the clinical studies required to fully develop and commercialize biomedical products and technologies. More recently, however, many investors in life science technologies have shown a preference toward financing the continued development of relatively mature technologies at established companies, rather than the higher-risk, emerging technologies under development at many small businesses. As a result, many small businesses need to have clinical data to attract sufficient third-party investment.

Definitions

For this funding opportunity announcement, Phase 1 and 2 clinical studies or trials refer to the common phases of a clinical trial. SBIR or STTR Phase I and II refer to the project phases of the SBIR/STTR programs.

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

• Evaluate and optimize the dose, formulation, safety, tolerability, usability, acceptability or pharmacokinetics of an intervention in healthy volunteers or the target population.
• Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., target engagement, dose-response trends, pharmacodynamic response) in a human "proof of concept" trial.
• Select or rank the best of two or more potential therapeutic approaches or dosing regimens to be evaluated in a subsequent trial, based on tolerability, biological activity, or preliminary clinical efficacy.

NIDDK recognizes that devices can differ greatly in terms of basic form and function, physiological bases for therapy, degree of invasiveness, etc. A pivotal device study, for example, could potentially be used in support of a new indication of an existing market approved device, or to provide evidence for a novel device design in support of a Pre-Market Approval (PMA), Humanitarian Device Exemption (HDE), 510(k) or 510(k) De Novo submission. Due to the broad scope of possible medical devices and the varied nature of the regulatory path, investigators considering applications to evaluate devices are strongly encouraged to contact Scientific/Research Staff as early as possible to discuss these issues and determine the suitability of their project for this FOA.

NIDDK will prioritize applications to develop novel interventions and discourages submission of applications to develop "me-too" strategies. NIDDK will also prioritize applications to develop interventions for indications for which there are no or few effective therapies or prevention strategies. While repurposing of already approved interventions may be supported under this FOA, NIDDK will not support studies meant to support label expansion.

Applicants should take note of the following:

(1) Effect Size: A trial will not be considered for funding under this FOA when its primary objective is to estimate intervention effect size to be used in power calculations for a future efficacy clinical trial. Effect size estimates based on small or short-term studies are often unreliable. Power for an efficacy trial should be based, whenever possible, on the Minimal Clinically Important Difference (MCID). The MCID is the smallest change in a treatment outcome that a patient would identify as important; it is often determined by surveying patients or their physicians.

(2) Secondary Aims: For drugs and biologics, issues of study feasibility and refinement of study procedures may be addressed as secondary aims in an exploratory clinical trial, but not as the primary aim. Examples of such secondary aims include:

• Collecting information on the utility of questionnaires, rating scales, or biomarkers
• Developing and refining standardized methods of assessing outcome
• Optimizing methods for identifying, recruiting, and retaining study participants
• Creating clinical trial infrastructure

(3) Multiple Trials: There may be multiple questions remaining to be answered before a Phase 3 trial can be designed and conducted. The proposed study is not required to address all potential questions but the applicant should clearly detail the total clinical development plan.

(4) Regulatory Approvals: If the intervention is a drug, biologic, or device, applicants should be able to provide information from the FDA on one of the following two scenarios:

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

(b) The protocol for the study and population proposed is exempt from an IND/IDE for the specific protocol, device, and patient population. Under this scenario, applicants must provide a copy of the exemption letter from the FDA, prior to funding. For devices, if the IRB has determined that the device is Non-Significant Risk, documentation from the IRB is acceptable, prior to funding.

Full IRB approval is not required at the time of application submission, but is required prior to funding. As such, NIDDK encourages investigators to begin these processes as early as possible. NIDDK also will require documentation of any other necessary regulatory approvals (e.g., Recombinant DNA Advisory Committee) prior to funding.

(5) Biomarkers:

• Applications are encouraged that utilize early signals of activity on biomarkers or clinical endpoints, or that mechanistically test the activity of an intervention in terms of its presumed target(s). However, in the absence of a suitable biomarker, clinical outcomes may be used.
• This FOA is not intended to support biomarker discovery.

(6) Adaptive Designs: The use of innovative and efficient study designs is encouraged, such as adaptive dose-finding designs, designs incorporating plans for sample size recalculation, and futility designs. Applications for Phase 1 clinical trials in the patient population are encouraged when appropriate, as are applications that encompass Phase 1 and Phase 2a clinical studies (early proof of mechanism or proof of concept). For medical devices, Early Feasibility and Traditional Feasibility study designs may include single-arm case series, on-off interventions (patients as own controls), device-device comparisons, comparisons to historic controls, comparisons to performance controls, or adaptive/Bayesian designs.

(7) Pharmacometrics: Applications seeking to obtain data needed for pharmacometric modeling are encouraged, with the ultimate aim of enabling the optimal design of a future efficacy trial of an intervention.

(8) Rare Diseases: Trials in rare diseases are encouraged. Innovative trial designs, including crossover designs and adaptive designs and N of one trials, may allow for the most efficient evaluation of the limited subjects available for study. For trials in rare diseases, it is especially important to ensure that the study design will meet the stated objectives, and the approach should carefully be justified.

(9) Patient Groups: Applicants are strongly encouraged to establish relationships with patient groups and solicit their input on recruitment, the clinical meaningfulness of the question under study, the relevance of the proposed clinical outcomes, and approaches to minimizing the burden on study subjects. See Section IV. 2. Letters of Support.

(10) NIH Resources: As appropriate, applicants are encouraged to make use of the following resources for clinical research including:

• Clinical and Translational Science Award (CTSA) program (https://www.ctsacentral.org )
• NIH Toolbox (http://www.nihtoolbox.org)
• PROMIS (http://www.nihpromis.org)

(11) Mobile Technologies: Applicants are encouraged to consider utilizing (at least experimentally) mobile technologies (e.g., wireless or remote) to facilitate data collection and protocol adherence on the part of research participants and study site staff.

(12) Consultation with NIDDK: Applicants are encouraged to consult with NIDDK Scientific/Research staff as plans for an application are being developed (see Section VII, Agency Contacts). This early contact will provide an opportunity to clarify NIDDK policies and guidelines as well as to discuss how to develop an appropriate project timeline and milestone plan, which is subject to peer review. As well, discussions regarding strategies for recruitment and inclusion of women and minorities are available.

(13) Applicants citing preclinical research should ensure it meets high scientific rigor guidelines (for reference see http://grants.nih.gov/reproducibility/index.htm).

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

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

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

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

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

3.

i. SBIR and STTR. Be a concern which is more than 50% directly owned and controlled by one or more individuals (who are citizens or permanent resident aliens of the United States), other business concerns (each of which is more than 50% directly owned and controlled by individuals who are citizens or permanent resident aliens of the United States), or any combination of these; OR

ii. SBIR-only. Be a concern which is more than 50% owned by multiple venture capital operating companies, hedge funds, private equity firms, or any combination of these. No single venture capital operating company, hedge fund, or private equity firm may own more than 50% of the concern; OR

iii. SBIR and STTR. Be a joint venture in which each entity to the joint venture must meet the requirements set forth in paragraph 3 (i) or 3 (ii) of this section. A joint venture that includes one or more concerns that meet the requirements of paragraph (ii) of this section must comply with 121.705(b) concerning registration and proposal requirements.

4. Has, including its affiliates, not more than 500 employees.

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

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

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

Definitions:

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

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

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

Phase I to Phase II Transition Rate Benchmark

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

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

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

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

Phase II to Phase III Commercialization Benchmark

In accordance with guidance from the SBA, HHS, including NIH, SBIR/STTR Programs are implementing the Phase II to Phase III 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 Phase III 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 receive New Phase I, Fast-track or Direct Phase II awards for a period of one year.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, may be allowed.

Applicant Organizations

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

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

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

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

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

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

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

Individuals involved in NIH-funded clinical trials must meet the requirements of ICH-Good Clinical Practice [GCP] training in accordance with the NIH Policy on Good Clinical Practice.

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

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

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

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

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

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.

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

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

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

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

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

Buttons to access the online ASSIST system or to download application forms 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.

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

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

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, preferably electronically, should be sent to:

John Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Room 7005
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: 301-594-7797
Fax: 301-480-3505
Email: NIDDKletterofintent@mail.nih.gov

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

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

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

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

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

The application must contain the following information, according to the instructions below, to provide evidence that the investigator(s) has planned a feasible clinical trial. The information provided here supports the Research Strategy and should not duplicate it. The following documents must be uploaded as separate pdf files with the names indicated below.

Other Attachments:

1. SBA Company registry

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

a. Navigate to the SBA Company Registry.

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

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

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

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

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

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

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

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

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

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

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

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

c. The authorized business official must sign the certification.

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

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

3. Clinical Protocol Synopsis is a required attachment

The filename "Clinical Protocol Synopsis.pdf" must be used for this attachment.

A clinical protocol synopsis is required for each planned clinical trial (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-015.html for the NIH Clinical Trial Definition). This is to provide a concise snapshot of the overall trial. It will be considered by reviewers, and is meant to supplement, not duplicate, the information provided in the Research Strategy.

The Clinical Protocol Synopsis is expected to include the following information which supports the Clinical Trial Protocol Overview section in the Research Strategy.

• Brief and/or Official Protocol Title.
• Intervention to be tested: A description of the intervention (to be tested, and a brief description of the protocol to be followed in each arm of the trial.
• Intervention / dosage and frequency: If applicable provide a description of the dose frequency and type of administration of the intervention(s).
• Primary and important secondary endpoints: Specify the endpoints for the primary and, if applicable, important secondary endpoints. Please provide a table showing the time points at which each endpoint will be assessed.
• Study Population: A description of the study population, including the sample size, gender, age, demographic group, required health status, and geographic location.
• Recruitment plans: A discussion of the availability of potential participants for the proposed study and the ability of participating sites to recruit and retain the proposed target number of participants. Describe approaches to be used for recruitment. If there is more than one site, provide a table showing the expected number and demographics of the population to be recruited at each site and overall.
• Retention plans: Approaches to be used for retention, cooperation and follow-up of those enrolled and to address any anticipated changes in the composition of the study population over the course of the trial.
• Group Assignment: Describe methods used to assign participants to study groups (treatment arms) and randomization.
• Subject Participation Duration: Time it will take for an individual participant to complete all study visits. When possible provide a brief snapshot of the protocol’s schedule of events capturing time points and planned activity at study visits. For example:
• Week 1 Screening/Baseline Visit (4 hours) - eligibility criteria, obtain informed consent, screening assessment(s), labs, etc.
• Week 2,4,6,8, Study Visit(s) (3 hours) intervention(s), assessment(s), labs, scan(s) etc.
• Week 12 and 18 Follow-up visits (3 hours) - assessment(s), labs, scan(s) etc.
• Week 24 End of study visit (2 hours) - assessment(s), labs, scan(s) etc.).
• Study Duration: Estimated time (in months) from when the study opens to enrollment until: (a) completion of data collection; and (b) final data analyses.
• Availability of Investigational Product (IP) and IND/IDE status: If applicable, provide a summary of the availability of IP and support for acquisition and administration. Please indicate the IND/IDE status of the IP, if applicable, and whether or not the investigators have had any interactions with the Food and Drug Administration (FDA). If the agent currently has an IND/IDE number, provide that information. Note that the NIDDK may request consultation with the FDA and the IND/IDE sponsor about the proposed clinical trial after peer review and prior to award.
• Eligibility Criteria
• FDA info on early feasibility studies: If applicable, provide FDA info available on early feasibility studies.
• A brief overview of the organizational structure, particularly the administrative, data coordinating, participating sites and any separate laboratory or testing centers.

Applications that lack the Clinical Protocol Synopsis are considered incomplete and will not be peer reviewed.

4. Clinical and Data Monitoring Plan is a required attachment

The filename "Clinical and Data Monitoring Plan.pdf" must be used for this attachment.

For each clinical trial proposed, create a document entitled "Clinical and Data Monitoring Plan".

Each Plan includes 2 parts: The Clinical Monitoring Plan for the quality assurance of the proposed clinical trial through clinical monitoring activities, and the Data Monitoring Plan for the quality controls proposed through data monitoring activities.

The NIH requirements for monitoring clinical trials as described below are in addition to the application's Data and Safety Monitoring Plan (DSMP) attachment on the PHS 398 Research Plan form which describes how patient safety in the trial will be monitored, and the regulatory requirement in 45 CFR 46 for on-going review and approval of all non-exempt human subjects research by the IRB of record.

Part A: The purpose of the Clinical Monitoring Plan is to verify that the clinical trial is being conducted, and documented in accordance with the Protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

• Describe the persons/entity responsible for conducting the monitoring (e.g., contracted Clinical Research Associate, Data Coordinating Center, Independent study monitor from the Clinical Coordinating Center).
• Describe the frequency of planned monitoring activities (e.g., Study Initiation, Interim Visits, Study Close Out), locations where the monitoring will occur (e.g., participating clinical sites, data center, clinical coordinating center) and what data will be reviewed.
• Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of the study intervention(s), including fidelity monitoring for behavioral interventions. Include methods to monitor study intervention and system to record and manage exceptions and deviations. If applicable, describe monitoring of participating facilities such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens. Include a description to assure that the investigational product(s) accountability and reconciliation are performed adequately during and at the end of the trial per applicable regulatory requirements.
• Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies the appropriate reporting to relevant authorities, including but not limited to the IRB of record, DSMB if one is assigned, FDA if applicable, institutional officials and the NIH.

Part B: The purpose of the Data Monitoring Plan is to ensure that validated systems and controls are in place to assure the integrity of the clinical research data being collected for the proposed study:

• Describe methods and systems for data collection (e.g., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and frequencies and any planned mitigation strategies in the event of noncompliance.
• Describe methods and systems to ensure data confidentiality and subject privacy.
• Describe process for locking the final trial datasets and the planned procedures on data access and sharing, as appropriate.

Applications that lack the Clinical and Data Monitoring Plan are considered incomplete and will not be peer reviewed.

5. The Milestone Plan is a required attachment

The filename "Milestone Plan.pdf" must be used for this attachment.

Applicants are required to provide detailed project performance and timeline objectives. This section must include an overview of the project timeline for the following general milestones, as applicable:

• Finalization of clinical protocol (with program agreement, if applicable)
• Registration of clinical trial in ClinicalTrials.gov
• Completion of regulatory approvals
• Enrollment of the first subject
• Enrollment and randomization, if applicable of 25%, 50%, 75% and 100% of the projected study population, including women, minorities and children (as appropriate)
• Completion of data collection time period
• Completion of primary endpoint and secondary endpoint data analyses
• Completion of final study report
• Reporting of results in ClinicalTrials.gov

These milestones will be negotiated at the time of the award, as appropriate.

Applications that lack the Milestone Plan are considered incomplete and will not be peer reviewed.

6. Common Data Elements Applicability is a required attachment

The filename "Common Data Elements Applicability.pdf" must be used for this attachment.

Applicants are required to provide a description of their plans to consider applicability of Common Data Elements (CDEs).

Investigators are encouraged to consult the Portal and to describe if NIH-supported CDEs will be used in the proposed clinical trial. If CDEs are not applicable, applicants are expected to explain why.

NIH encourages the use of common data elements (CDEs) in clinical research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.

Applications that lack the 'Common Data Elements Applicability' attachment are considered incomplete will not be peer reviewed.

7. Statistical Analysis Plan

The filename "Statistical Analysis Plan.pdf" must be used for this attachment.

The applicant(s) should describe the statistical methods to be used, including the sample size and power calculations, plans for the primary and secondary analyses, and any re-specified interim analyses. The plan is critical to knowing whether applicants have selected the correct cohort size and/or are using the most appropriate methods to analyze the data and make the correct conclusions at the end of the study.

Applications that lack the Statistical Analysis Plan are incomplete and will not be peer reviewed.

8. Investigator Brochure or Package Insert

The filename "Investigator Brochure or Package Insert.pdf" must be used for this attachment.

The Investigator Brochure or package insert may be attached for a clinical trial testing a drug or biologic.

9. Material safety data sheet (MSDS)

The filename "Material safety data sheet (MSDS).pdf" must be used for this attachment.

Labeling information or summary of safety information from prior studies may be attached for a clinical trial testing a significant risk investigational device for which an application for a new Investigational Device Exemption (IDE) will be submitted.

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

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

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

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

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

Specific Aims: The specific aims of the exploratory clinical trial must be clearly and concisely presented. The primary and major secondary hypotheses to be evaluated must be clearly stated.

Research Strategy:

Clinical Trial Protocol Overview: For the proposed clinical trial, this section should include:

• A summary of the study protocol’s objectives describing the scientific rationale and clinical need for the trial, the condition or focus of study, the trial’s potential impact, an assessment of the previous preclinical and clinical studies and their quality, including a discussion of information or data from preliminary studies that address the need for and feasibility of the proposed trial.
• A description of the study design which should include the following information:
• Primary Purpose (e.g., Treatment, Prevention, etc.)
• Type of Intervention (e.g., Drug, Biologic, Device, Behavioral)
• Study Phase (e.g., Pilot, Phase 1, 1/2, 2)
• Interventional Model (e.g., single-group, parallel, cross-over, factorial)
• Masking (e.g., open, single blind, double blind)
• Allocation (e.g., single-arm, randomized, non-randomized)

NIH recognizes the role of both effectiveness/pragmatic versus efficacy trials and understands that all elements won t apply to all trial types (e.g. frequent patient visits, 100% source data verification, frequent site monitoring) for example for large simple effectiveness trials. Applicants should ensure applicable elements are provided based on the type of trial planned (e.g., efficacy, effectiveness, randomized registry or pilot trials).

Applicants planning Phase 2 clinical trials that require investigational new drug (IND) or investigational device exemption (IDE) applications should provide elements that are consistent with the requirements of the Food and Drug Administration

(FDA) IND or IDE. A proposed template for such studies can be found here http://osp.od.nih.gov/sites/default/files/Protocol_Template_05Feb2016_508.pdf

Significance and Biological Relevance:

The significance and, when applicable, the biological relevance of the proposed clinical trial must be clearly stated. It is particularly important that there be discussion of how the trial will test the primary hypothesis and how the results of the trial (positive or negative) will ultimately affect clinical practice. The application should explain why the proposed trial is necessary to plan for subsequent studies.

Innovation:

The proposed technology/product should be compared with other existing approaches. If the proposed therapeutic is improving over early generations (that may or may not have been marketed), potential advantages should be clearly described.

Prior Studies and Rationale for Development:

Summarize the specific aims of the preliminary work that forms the basis for this Phase II application, quantitative milestones (a quantitative definition of success) for each aim, the importance of the findings, and emphasize the progress made toward their achievement. Pilot studies, done with non-SBIR funds, that show the need for and the feasibility of the trial should be discussed. The rationale for an exploratory trial must be based on (1) an unmet medical need; (2) a plausible biological mechanism; (3) non-clinical (in vivo and/or in vitro data); and (4) preliminary clinical data. Although all of these criteria may not be met depending on the phase of development, the applicant should demonstrate that there is a robust scientific foundation to justify the proposed trial. Applicants should discuss the limitations of any data presented. Likewise, any prior clinical research cited should be scientifically rigorous.

Applications should address the reasons for consideration of the intervention. This may include preclinical in-vitro and in-vivo data. Animal efficacy data should be included in the rationale only when the model and read-out are considered sufficiently associated with the human condition, and only if the experiments sufficiently meet criteria outlined in the aforementioned NIH guidelines. Other considerations are toxicology data (e.g., whether the FDA has found the toxicology data to be acceptable to proceed with the proposed trial); medicinal chemistry/pharmacology data (e.g., whether the formulation is feasible and the pharmacokinetics acceptable for use as intended in the trial); regulatory considerations (e.g., details on FDA, European Medicines Agency (EMA), and other agencies' evaluations; discussion of the likelihood of regulatory approval based on acceptability of endpoints, orphan drug status, etc.); public health impact if subsequent efficacy trials are conducted and positive; ethical dimensions; and patient perspectives on acceptability of the proposed intervention. Characteristics of any preliminary research results provided in support of the proposed project, whether conducted by the applicant or others, should be described in the application so that peer review may evaluate the strength of the supporting evidence. The following items should be discussed if applicable to the proposed project.

Experimental design:

• Rationale for the selected models and endpoints (animal and/or cellular)
• Adequacy of the controls
• Route & timing of intervention delivery / dosing
• Justification of sample size, including power calculation
• Statistical methods used in analysis and interpretation of results

Minimizing bias:

• Methods of blinding (allocation concealment and blinded assessment of outcome)
• Strategies for randomization and/or stratification
• Reporting of data missing due to attrition or exclusion
• Reporting of all results (negative and positive)

Results:

• Independent validation/replication, if available
• Robustness and reproducibility of the observed results
• Dose-response results
• Verification that interventional drug or biologic reached and engaged the target at optimal concentrations

Interpretation of results:

• Alternative interpretations of the experimental data
• Relevant literature in support or in disagreement with the results
• Discussion of effect size in relation to potential clinical impact
• Potential conflicts of interest
• If preclinical data (e.g., animal studies) do not meet the rigor guidelines, the applicant should discuss the limitations of those data.

Letters of Support: Applicants are encouraged to include letters from patient organizations or other supporting documentation to show that patients were included as partners in the concept development and design of the trial. Applicants are also encouraged to include documentation of the commitment of any subcontractors and consultants as well as service agreements for personnel or facilities. Letters of commitment must be co-signed by the business official of the collaborating center.

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

Note that Phase I SBIR/STTR Appendix materials are not permitted.

The following additional document should be included in the Appendix as a single .pdf file:

• The Complete Clinical Trial Protocol (Required)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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), SBA Company Registry, eRA Commons, and Grants.gov.

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.

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy -.

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

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?)

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?

Does the project cite prior relevant trials or systematic reviews that would help to justify why this trial is needed and inform its design?

Is there a sufficient body of preclinical or clinical research of high scientific rigor to support the study rationale for the phase of development proposed?

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

Is there convincing evidence that there is equipoise in the medical and patient communities and the intervention is ready for clinical development?

Is it clear why the proposed exploratory trial is essential to inform the design and implementation of subsequent steps in the evaluation of the intervention?

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?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have clinical trial-specific expertise and experience; the ability to organize, manage and implement the proposed clinical trial and meet study milestones and timelines? Do they have appropriate capacity in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate?

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?

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

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

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

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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? 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 children, justified in terms of the scientific goals and research strategy proposed?

If potential threats to the data integrity are known about the proposed research, will these threats affect the feasibility of the proposed research?

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 clinical and statistical hypothesis being tested? 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? Is there a plan to complete data analysis within the proposed period of the award?

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 data collection? Is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed?

Is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results?

Are planned analyses and statistical approach appropriate for the proposed study design?

Is there evidence that all necessary regulatory approvals have been obtained?

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?

Does the information provided in the application give reasonable assurance that the target sample size can be enrolled in the timeframe proposed?

Have necessary agreements with participating industry partners, if necessary for the clinical trial, been established? Is there documentation of the commitment of any subcontractors and consultants as well as service agreements for personnel and facilities?

To what extent does the applicant SBC have the ability to address regulatory issues, either through their own staff members or through appropriate arrangements with external regulatory consultants?

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

Clinical Trial Sites or Centers

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 potential complexities of executing the clinical trial in these sites?

If multi-sites/centers are proposed, 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?

Clinical Data Monitoring Plan

Are the procedures for clinical data monitoring and quality control of data adequate? Are standardized systems and controls in place for data monitoring to ensure data integrity and to assess the effect of the intervention?

Study Timeline and Milestones

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 appropriate, evaluative milestones clearly defined for the aims associated? Are the milestones feasible and quantifiable with regard to specific aims and timeline? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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

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?

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

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

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

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.

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.

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.

For Phase IIB Applications, the committee will consider the progress made in the last funding period.

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

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

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).

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.

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.

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

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

As part of the scientific peer review, all applications:

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 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.

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

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

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

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

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

ClinicalTrials.gov: If an award provides for one or more clinical trials, by law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH encourages 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 the application as well as 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). Information about DSMPs is also available on the NIDDK website: http://www.niddk.nih.gov/research-funding/process/human-subjects-research/policies-for-clinical-researchers/data-safety-monitoring-plans/Pages/data-and-safety-monitoring-plans.aspx.

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 participant recruitment based on projected milestones.

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

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

Not Applicable

NIH requires that SBIR/STTR grantees submit the following reports within 90 days of the end of the grant budget period unless the grantee is under an extension. When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

For details about each specific required report, see Part III. Section 5, "SBIR/STTR Award Guidelines, Reporting Requirements, and Other Considerations, in the Supplement Grant Applications For All Competing Applications and Progress Reports.

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

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)

Telephone: 301-945-7573

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

For Clinical Trials in the area of Diabetes, Endocrinology, & Metabolic Diseases:

Guillermo Arreaza-Rubin, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-4724
Email: arreaza-rubing@niddk.nih.gov

For Clinical Trials in the area of Digestive Diseases and Nutrition:

Christine Densmore, M.S.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-8714
Email: densmorec@extra.niddk.nih.gov

For Clinical Trials in the area of Kidney, Urologic, and Hematologic Diseases:

Marva Moxey-Mims, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301- 594-7717
Email: moxeymimsm@extra.niddk.nih.gov

Thomas A. Tatham, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-3993
Email: tathamt@niddk.nih.gov

Pamela Love
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-435-6198
Email: lovepa@mail.nih.gov

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

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

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