Leveraging Artificial Intelligence (AI) tools for Substance Use Disorders (SUD) drug discovery and development (R43/R44 - Clinical Trial Not Allowed)

Leveraging Artificial Intelligence (AI) tools for Substance Use Disorders (SUD) drug discovery and development (R43/R44 - Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). This Funding Opportunity Announcement (FOA) solicits grant applications from small business concerns (SBCs) to develop Artificial Intelligence (AI)-related technologies for drug discovery and drug development for Substance Use Disorders (SUD), excluding alcohol use disorder.

Expired RFA-DA-22-021: Leveraging Artificial Intelligence (AI) tools for Substance Use Disorders (SUD) drug discovery and development (R41/R42 - Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. 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 Drug Abuse ( NIDA ) Funding Opportunity Title Leveraging Artificial Intelligence (AI) tools for Substance Use Disorders (SUD) drug discovery and development (R41/R42 - Clinical Trial Not Allowed) R41 / R42 Small Business Technology Transfer (STTR) Grant - Phase I, Phase II, and Fast-Track July 07, 2021 - Notice of Correction to Application Types Allowed for RFA-DA-22-021.

See Notice NOT-DA-21-048 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity RFA-DA-22-019 - Leveraging Artificial Intelligence (AI) tools for Substance Use Disorders (SUD) drug discovery and development (R43/R44 Clinical Trial Not Allowed) See Section III. 3.

Additional Information on Eligibility .

Assistance Listing Number Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) seeks grant applications from small business concerns (SBCs) to develop Artificial Intelligence (AI)-related technologies for drug discovery and drug development for Substance Use Disorders (SUD), excluding alcohol use disorder Open Date (Earliest Submission Date) Letter of Intent Due Date(s) No late applications will be accepted for this Funding Opportunity Announcement.

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s). Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s) Required Application Instructions It is critical that applicants follow the SBIR/STTR (B) Instructions in the SF424 (R&R) SBIR/STTR Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Funding Opportunity Description SUDs are a set of complex and chronic diseases with an interplay between genetic and environmental factors. In the constellation of SUDs, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) provides a framework that includes ten separate classes of substances and covers 11 different criteria for their diagnosis.

Currently, there are a limited number of pharmaco-therapeutics for either tobacco use disorder (TUD) or opioid use disorder (OUD) approved by the Food and Drug Administration (FDA). Additionally, there are still no approved therapies for other SUDs, such as stimulant or cannabis use disorders, despite the current understanding of neurological mechanisms and treatments being clinically evaluated.

The costs and time to develop a new molecular entity (NME) from the discovery phase to a successful registration have been increasing steadily over the years. Multiple stakeholders, including government, academia, and the pharmaceutical industry are searching for ways to increase efficiency in research and development (R&D) to save time and money in drug development.

Non-traditional drug development approaches and novel predictive analyses may provide additional venues to create innovative insights leading to discovering novel targets, treatments, and mechanisms of action to treat SUD.

Artificial Intelligence (AI) has become central to a growing number of businesses and incorporated in their business models and has led to the acceleration and advanced development of the applications, such as AI-related powered chatbots, eCommerce, Communication, manufacturing, cybersecurity, surveillance, and smart technologies.

Such growth results from several technological developments, namely, increased computational capacity, improved and advanced neural network algorithms, and more available diverse, complex sets of data ( Big Data ). AI technologies can extract concepts and relationships from Big Data, learn independently from the data patterns, and significantly augment human capabilities.

AI technologies include computer vision, robotics, machine learning (ML), including deep and reinforcement learning, and natural language processing (NLP). In health care, AI is being investigated to analyze patient Big Data, such as electronic health records (EHR) of historical treatments and current care of patients to create more effective and better patient outcomes along with identifying new diagnostic tools and novel analyses.

Recent partnerships between advanced computational approach-based companies and pharmaceutical companies are utilizing AI technologies to improve therapeutic research and development from early discovery to clinical trials.

In 2020, the notice NOT-OD-21-011 demonstrated the continued National Institutes of Health (NIH) and National Science Foundation (NSF) interest in the growing area of AI technology use to improve science and public health.

Adopting AI and related technology development may allow researchers to take advantage of such untapped advancements and identify complex patterns in the consumer and environmental data relevant to SUD drug development.

Applications of AI-related tools to drug development are being increasingly investigated in all stages of the therapeutic pipeline, ranging from medicinal chemistry to clinical trials, with the ultimate goal of improving the R&D efficiency. AI technologies have also assisted medicinal chemistry areas through computer-aided novel drug design for the NME characteristics such as the Lipinski rules.

In silo screens have been performed when the three-dimensional structural data of a protein target can be utilized in drug-docking studies. With the observation of novel & multigenic targets for common disorders, traditional one-disease-one-target dominance is being reconsidered for polypharmacology-based therapeutics.

The polypharmacology strategy can also include AI-related predictions of adverse drug reactions and computational toxicology. AI technology use can accelerate drug repurposing of clinical-stage therapeutics, which have the advantage of moving directly into clinical trials, thereby saving more time and money.

For First in class NMEs by either target-based or phenotypic drug discovery, researchers found that phenotypic screening yielded significantly more of these novel NMEs. While the phenotypic approaches have the advantage of unbiased target investigation, this approach does require the extra step of target deconvolution analyses where AI technologies can assist in image analyses and feature analyses.

In the investigation of complex or unmet disorders, the omics -based analyses can yield new drug targets and new biomarkers. Additional areas where AI technologies are in use include reviewing biomedical research literature for many important areas (e.g., reproducibility, human evidence, target identification, data repositories for genetics, biomarkers identification, clinical trial design, patent searches).

The incorporation of AI-related technologies has had recent successes and is predicted to accelerate traditional and innovative areas of SUD drug development. In 2020, the first reported AI-developed therapy is being used in clinical trials to treat obsessive-compulsive disorder (OCD) patients.

The development time for this AI-based drug development was 12 months, which is significantly shorter than the routine exploratory research phase of drug development that can take up to five years. This proof of concept exemplifies that AI-based technologies can drastically save many years spent on drug profiling and hold the potential to cut down the expense of the drug development process as well.

AI can be leveraged to develop a set of novel biomarkers and secondary outcomes for clinical SUD studies. In addition, AI technologies may analyze the basic science of SUD models and patient data separately, then facilitate the linking of this data with clinical outcomes to help optimize personalized treatments of SUD.

These approaches hold the additional promise to decrease drug development cost and time by providing quantitative values to assess candidate molecules' efficacy, even before performing laboratory experiments or pre-clinical tests. AI platforms may help normalize and annotate Big Data resources, including hundreds of millions of human biological, pharmacological, and clinical data points.

The development of AI network-based algorithms and the analyses of these data may identify precision medicine approaches and repurpose existing NMEs for SUD indications. AI-related predictions of personalized medicine (e.g., identifying patients who would potentially benefit more from the drug or experience a more significant side-effect profile) may be particularly useful in this context.

This Funding Opportunity Announcement (FOA) aims to develop AI technologies specifically for the SUD drug development, addressing knowledge discovery, drug discovery, drug testing, drug repurposing, and clinical trial designs that can be subject to automation. Applications focusing on alcohol use disorder or pain as the primary indication will not be supported under this National Institute on Drug Abuse (NIDA) funding opportunity.

Areas of interest include, but are not limited to, the development and utilization of AI-based tools in the following areas for SUD drug discovery and development: 1.

Drug target identification and validation: (a) AI-driven tools and platforms that automate the transformation of diverse streams of biomedical and healthcare data, such as longitudinal EHR, next-generation sequencing, and other -omic data into mechanistic computer models to be representative of individual patients.

(b) AI models using biomedical and clinical data that can draw novel insights about drug candidates and model the whole biological systems to help identify novel pathways, targets, and biomarkers. 2. Target-based and phenotypic drug discovery: (a) AI-related systems that can design new molecules employing phenotypic, high-content screening data along with assessing their potency, selectivity, and binding affinity.

(b) AI-based modeling at each stage of the process, from the hit identification and expansion through lead design/optimization to absorption, distribution, metabolism, and excretion (ADME)/toxicity predictions. (c) AI technology platforms that work with data points obtained from different studies of high-content, low-throughput phenotypic assays, high-throughput screening, structure-based design, and traditional computational methods.

3. Polypharmacology discovery: (a) AI algorithms that include data from studies of the genome, proteome, metabolome, and the lipidome of the biological samples to evaluate the complex biological networks playing roles in SUD and help identify medications for specific patient populations and sift through the drug candidates that are likely to fail.

(b) AI-systems that probe vast chemical spaces and identify the most promising drug candidates. (a) AI tools that analyze and visualize Big Data (e.g., biomedical, clinical, research) and identify new patterns and insights to understand how drugs work and which of them are useful in satisfying unmet medical needs in the SUD area.

(b) AI based platforms utilizing Big Data resource includes hundreds of millions of human subjects, biological, pharmacological, and clinical data points, normalized and annotated to build network-based algorithms to repurpose existing drugs or identify drug candidates or identify drug targets related to SUD indications. 5.

Biomarkers development: (a) AI tools that identify molecular signatures and potential biomarkers for assessing the drug response, advancing deep-learning screens of biomarkers from patient data, and multi-omic modeling approaches utilizing real-world biomedical data, including gene expression, protein interaction networks, and clinical records.

(b) AI based models that identify potential responders to a molecular targeted therapy before the drug is tested in humans. 6. Predictions of Adverse Drug Reactions: (a) Machine learning workflow that can enhance predictions of Adverse Drug Reactions (ADRs) through drug-gene interactions.

7. Clinical Trial Design: (a) AI-based systems that correlate large and diverse datasets such as EHRs, the medical literature, and trial databases for the improved patient trial matching (cohort composition) and recruitment before a trial starts, as well as for monitoring patients automatically and continuously during the trial, thereby allowing improved adherence control and yielding more reliable and efficient endpoint assessment.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects.

Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Web site at http://www. drugabuse.

gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects .

Points to Consider Regarding Tobacco Industry Funding of NIDA Applicants: The National Advisory Council on Drug Abuse (NACDA) encourages NIDA and its grantees to consider the points it has set forth with regard to existing or prospective sponsored research agreements with tobacco companies or their related entities and the impact of acceptance of tobacco industry funding on NIDA's credibility and reputation within the scientific community.

Please see http://www. drugabuse. gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding- for details.

Data Harmonization for Substance Abuse and Addiction via the PhenX Toolkit: NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.

phenxtoolkit. org). Please see NOT-DA-12-008 ( http://grants.

nih. gov/grants/guide/notice-files/NOT-DA-12-008. html ) for further details.

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

Award Information 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 (Phase I), New (Fast-Track) 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.

Not Allowed: Only accepting applications that do not propose clinical trials Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NIDA intends to commit $3,000,000 in FY 2022 to fund 8-10 awards in response to this FOA and the companion RFA-DA-22-019 .

Total funding support (direct costs, indirect costs, fee) normally may not exceed $259,613 for Phase I awards and $1,730,751 for Phase II awards. NIH has received a waiver from SBA, as authorized by statute, to exceed these total award amount hard caps for specific topics. The current list of approved topics can be found at https://sbir.

nih. gov/funding#omni-sbir . Navigate to the Program Descriptions and Research Topics document, Appendix A or the current "SBA approved topics list for budget waivers".

Applicants are strongly encouraged to contact program officials prior to submitting any application in excess of the hard caps listed above and early in the application planning process. In all cases, applicants should propose a budget that is reasonable and appropriate for completion of the research project. According to statutory guidelines, award periods normally may not exceed 1 year for Phase I and 2 years for Phase II.

Applicants are encouraged to propose a project duration period that is reasonable and appropriate for completion of the research project. 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 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: 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; 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; 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 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 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.

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. 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. 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 must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted.

Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission. Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number.

After obtaining a DUNS number, applicants can begin both SAM, SBA Company registry, and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually .

The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. SBA Company Registry See Section IV.

Application and Submission Information , SF424(R&R) Other Project Information Component for instructions on how to register and how to attach proof of registration to your application package. Applicants must have a DUNS number to complete this registration. SBA Company registration is NOT required before SAM, Grants.

gov or eRA Commons registration. eRA Commons - Applicants must have an active DUNS number number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants.

gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants. gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

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

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For the STTR program, the PD(s)/PI(s) may be employed with the SBC or the single, partnering non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual.

Each PD/PI must commit a minimum of 10% effort to the project and the PD/PI must have a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration.

The SF424 (R&R) SBIR/STTR Application Guide should be referenced for specific details on eligibility requirements. For institutions/organizations proposing multiple PDs/PIs, see Multiple Principal Investigators section of the SF424 (R&R) SBIR/STTR Application Guide. This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization.

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

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

A Phase I awardee may submit a Phase II application either before or after expiration of the Phase I budget period, unless the awardee elects to submit a Phase I and Phase II application concurrently under the Fast-Track procedure.

To maintain eligibility to seek Phase II or IIB support, a Phase I awardee should submit a Phase II application, and a Phase II awardee should submit a Phase IIB application, within the first six due dates following the expiration of the Phase I or II budget period, respectively.

Contractual/Consortium Arrangements In Phase I and Phase II, at least 40% of the research or analytical effort must be performed by the small business concern and at least 30% of the research or analytical effort must be performed by the single, partnering research institution.

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

A small business concern may subcontract a portion of its SBIR or STTR award to a Federal laboratory within the limits above. A Federal laboratory, as defined in 15 U.S.C. 3703, means any laboratory, any federally funded research and development center, or any center established under 15 U.S.C.

3705 & 3707 that is owned, leased, or otherwise used by a Federal agency and funded by the Federal Government, whether operated by the Government or by a contractor. The basis for determining the percentage of work to be performed by each of the cooperative parties in Phase I or