It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) 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

Pre-Application Webinar

NIH anticipates holding a pre-application webinar to which all interested prospective applicants are invited. NIH and FDA Program and Review staff persons will explain the goals and objectives of the Tobacco Centers of Regulatory Science (TCORS) for Research Relevant to the Family Smoking Prevention and Tobacco Control Act funding opportunity announcement (FOA), discuss the application peer review process, and answer questions. Information about this pre-application conference call will be available at https://prevention.nih.gov/tobacco-regulatory-science-program.

Purpose

This Funding Opportunity Announcement (FOA) invites cooperative agreement (U54) applications for Tobacco Centers of Regulatory Science (TCORS) for research relevant to the Family Smoking Prevention and Tobacco Control Act. The overall TCORS program objective is to conduct programs of multidisciplinary research that will inform the manufacture, distribution, and marketing of tobacco products related to the regulatory authority of the Food and Drug Administration (FDA) Center for Tobacco Products (CTP). The research findings generated from this FOA are expected to provide additional scientific data to inform the regulation of the tobacco products to protect public health.

The awards under this FOA will be administered by NIH using designated funds from FDA CTP for tobacco regulatory science mandated by the Family Smoking Prevention and Tobacco Control Act (FSPTCA), Public Law 111-31. NIH and FDA have formed an interagency partnership to foster research relevant to tobacco regulatory science within the framework of the Tobacco Control Act. As cooperative agreements, NIH and FDA will be substantially involved with the awardees. Separate FOAs will solicit cooperative agreement applications for a U54 Coordinating Center (Center for Coordination of Analysis, Science, Enhancement, and Logistics (CASEL) for this program and a U01 Center for Rapid Surveillance of Tobacco (CRST). CASEL will provide the necessary scientific leadership and administrative framework to facilitate interactive and integrative collaboration and communication among the awardees of the individual TCORS, NIH and FDA staff, and other FDA-funded investigators, as appropriate.

Consistent with the FDA CTP mission, this FOA encourages research applications that address such Scientific Domains as: 1) understanding the composition and design of tobacco products, 2) approaches that test the toxicity of tobacco smoke, aerosol, or specific constituents, 3) the effect of tobacco product characteristics on addiction and abuse liability, 4) the short- and long-term health effects of tobacco products, 5) understanding the knowledge, attitudes, perceptions, and behaviors related to tobacco product use, 6) understanding how to effectively communicate the health effects of tobacco products, 7) the influences of tobacco marketing, and 8) understanding the impact of potential FDA regulatory actions.

Background

Since 2009, FDA has regulated cigarettes, smokeless, and roll-your-own tobacco. FDA finalized a rule, effective August 8, 2016, to regulate all tobacco products including electronic nicotine delivery systems or ENDS (e.g., vapes, vaporizers, vape pens, hookah pens, electronic cigarettes (e-cigarettes or e-cigs), and e-pipes), cigars, pipe tobacco, gels, hookah (waterpipe) tobacco, and future tobacco products. Tobacco products are subject to provisions outlined in the FD&C Act. FDA also has the authority to develop tobacco product standards, when appropriate for the protection of public health.

A full description of the FSPTCA can be found at: https://www.fda.gov/tobacco-products/rules-regulations-and-guidance/family-smoking-prevention-and-tobacco-control-act-overview.

Research Objectives and Administrative Structure Requirements

The overall TCORS cooperative agreement research program objective is to conduct programs of multidisciplinary research that will inform FDA’s tobacco product regulatory activities. The TCORS program will lead the establishment of a broad national scientific base of tobacco regulatory research. Although a vast and sound science base exists with regards to numerous areas related to the FSPTCA, new research will provide additional science for FDA to consider as it conducts regulatory activities. Essential elements of TCORS applications include at least 3 discrete hypothesis driven Research Projects with a scientific Integrative Theme, an Administrative Core, a Career Enhancement Core, and optional cores as needed and justified. Research integrated across projects, where findings from one major project inform or complement those in another, is required.

Disciplinary integration within a TCORS, and within projects (where feasible) is also encouraged. Disciplinary diversity in a TCORS must support the objectives of the science and not merely reflect the training of the scientists. Meaningful collaboration is permitted across geographically separate sites within a funded TCORS. Each TCORS funded under this announcement is expected to work with NIH and FDA staff to collaborate with other TCORS, a designated Coordinating Center, and a Center for Rapid Surveillance of Tobacco (CRST), on a regular basis to share information, assess scientific progress in the field, identify new research opportunities, participate in one or more cross-site scientific working groups, address research gaps, and resolve areas of scientific disagreement.

Part A. Research Objectives Requirements

TCORS INTEGRATIVE THEME

Applicants will be required to identify an overall Integrative Theme for their proposed TCORS. The level of specialization in different dimensions of regulatory tobacco research will vary with each TCORS, e.g., topics, populations, levels of analysis, and types of research (e.g., cell culture, animal models, or human models; cross-sectional or longitudinal study designs). However, TCORS should focus thematically on areas in which there are significant gaps in knowledge--where focused, collective, interdisciplinary efforts could make the greatest difference in reducing tobacco use and its adverse health consequences through the regulation of the manufacture, distribution, and marketing of tobacco products.

Individual TCORS may vary in their breadth or concentration across research foci (e.g., molecular to population-based research)*. Integrative Themes may coalesce around a research gap that is tobacco product- or constituent-specific (e.g., cigars, flavors)* that addresses Scientific Domains (e.g., addiction, toxicity, effects)*, or may represent an integrative approach to generating data needed to regulate tobacco in a way that reduces use and harm in populations that experience greater tobacco related health disparities *. It is expected that the TCORS will facilitate more rapid advances in knowledge than would be possible by depending on individual investigators working in relative isolation.

*NOTE: Examples are for illustrative purposes and do not indicate particular priorities.

SCIENTIFIC DOMAINS

Consistent with the FDA CTP mission, this FOA encourages research applications that address such Scientific Domains as: 1) understanding the composition and design of tobacco products, 2) approaches that test the toxicity of tobacco smoke, aerosol, or specific constituents, 3) the effect of tobacco product characteristics on addiction and abuse liability, 4) the short- and long-term health effects of tobacco products, 5) understanding the knowledge, attitudes, perceptions, and behaviors related to tobacco product use, 6) understanding how to effectively communicate the health effects of tobacco products use, 7) the influences of tobacco marketing, and 8) understanding the impact of potential FDA regulatory actions.

FDA encourages research studies to include, where appropriate to the research question, vulnerable populations, including (but not limited to):

• youth and young adults,
• those from lower socioeconomic backgrounds (e.g., those with lower household incomes or lower educational attainment),
• racial or ethnic minorities,
• sexual and/or gender minorities,
• rural populations,
• those pregnant or trying to become pregnant,
• active-duty military or veterans, those who are or have been incarcerated,
• and those with mental health conditions or substance use disorders.

If a vulnerable population will be included, applicants will be expected to identify the population and how the population is important to the research question, considering the impact on population health. Health disparity considerations can be incorporated into all the topics below.

A goal of the TCORS program will be to support a portfolio that is balanced across the Scientific Domains below. Any single project can focus on one or more of these domains. However, applications must propose a program that includes two or more of the following Scientific Domains across all projects:

Note: Addressing many/all Scientific Domains in an individual TCORS is not advantageous. What is important regarding Scientific Domains is to demonstrate how the research proposed integrates with the center's overall theme to inform tobacco regulatory activities.

Product Composition and Design Understanding the chemical constituents in tobacco products and the methods for measuring them across products with diverse characteristics**. Priorities include:

• Determination of smoking, heat-generating, or aerosol-generating regimen to be used for measuring harmful and potentially harmful constituents (HPHC) in smoke (e.g., cigarettes, pipes) and aerosols (e.g., ENDS, heated tobacco products);
• Identification, quantification, and determination of the formation of the chemical constituents of novel tobacco products including ENDS aerosols or other aerosol-generating tobacco products;
• Determination of relationship between the nonadjustable or user adjustable design parameters of heating element temperature/wicking material/air flow of ENDS devices or other aerosol-generating tobacco products and constituent yields/particle size in the aerosol;
• Determination of the relationship between waterpipe materials/design of waterpipe devices and constituent yields in the waterpipe smoke;
• Development of internationally recognized analytical methods applicable to various tobacco types;
• Development of methods to evaluate nicotine release across different smokeless tobacco products (e.g., snuff/dip, snus, chew);
• Characterization of the antimicrobial activity of propylene glycol (PG), vegetable glycerin (VG), and flavor ingredients;
• Determination of relationship between humectant concentration or type and water activity of waterpipe, pipe, and cigar tobacco;
• Characterization of the relationship between intrinsic/extrinsic factors (e.g., battery design; environmental conditions, use conditions [e.g., changing battery, charging]) and ENDS battery overheating, fire, or explosion incidents.

Toxicity Understanding how tobacco products and changes to tobacco product characteristics** affect their potential to cause morbidity and mortality in users and nonusers through secondary exposure; including animal (in vivo) and cell culture (in vitro) models, as well as novel alternative toxicology approaches that test the toxicity of tobacco smoke (other than cigarette), aerosols, or specific constituents in tobacco and the tobacco product. Priorities include:

• Evaluation of toxicity from exposures to complex mixtures of tobacco-related constituents in ENDS aerosol, waterpipe smoke, cigar smoke, and smokeless tobacco using toxicological assays such as in vivo, in silico, as well as in vitro models that are more physiologically relevant to humans;
• How product design characteristics** (variation(s) in those characteristics**) impact constituent exposure and toxicity from tobacco products;
• Biomarkers to assess exposure, as well as biomarkers to assess harm or toxicity of products other than conventional cigarettes, including ENDS and waterpipes; and toxicological impact of nicotine, flavors, and other constituents across different concentrations, patterns of use behavior (dual/poly use, product switching) and routes of exposure.

Addiction Understanding the effect of tobacco product characteristics** on addiction and abuse liability across populations. Priorities include:

Impact of changes in tobacco product characteristics** (such as flavors, product design, and nicotine formulation) on dependence and use behaviors;

• Correlation of ENDS use behaviors with pharmacokinetic and pharmacodynamics effects of nicotine and other HPHCs delivered by ENDS; and the relationship between specific flavor categories in ENDS (including, but not limited to, tobacco, menthol, fruit, and sweet/dessert) and adult users interest in cessation as well as quit attempts, reduced cigarette use and/or switching to potentially less harmful tobacco products;
• ENDS users biomarkers of exposure during ENDS experimentation, regular ENDS use, and dual use of ENDS and cigarettes (with reduced cigarettes per day and maintaining cigarettes per day).
• Impact of synthetic coolants in ENDS and cigarettes on product abuse liability (e.g., nicotine pharmacokinetics, product subjective effects), dependence, and use behaviors (such as progression to regular product use, switching, and cessation).

Health Effects Understanding the short- and long-term health effects of tobacco products (excluding conventional cigarettes) with priority on longitudinal data. Areas of interest include cardiovascular, cancer, neurological (e.g., seizures), oral, reproductive, and respiratory health effects (including inflammation and lung disorders (e.g., asthma, COPD)). Priorities include:

• Impact of tobacco product characteristics** (such as e-liquid non-tobacco flavors, product design, e-liquid nicotine concentration, nicotine formulation) on human health;
• Impact of novel product use (e.g., ENDS, heated tobacco products) on biomarkers of exposure and biomarkers of potential harm;
• Association between exclusive products other than conventional cigarette-related exposures and disease risk; association between dual/poly use of tobacco products and disease risk;
• Identifying biomarkers of potential harm to assess short- and long-term health effects of tobacco products, with a focus on products other than conventional cigarettes, including deemed products or other novel products;
• Association between cigar sub-types use and disease risk;
• Association between waterpipe and waterpipe materials use and disease risk.

Behavior Understanding the knowledge, attitudes, perceptions, and behaviors related to tobacco product use and the impact of tobacco product characteristics** on behaviors across populations, as appropriate. Priorities include:

• The impact of tobacco product characteristics** (such as e-liquid flavors, product design, nicotine concentration, and formulations) on tobacco use preferences and behaviors (such as intentions to use, experimentation, initiation, progression, dual/poly tobacco use, switching, and cessation-related behaviors) among youth, young adults, and adults;
• Innovative methods, measures, and study designs to assess tobacco use knowledge, attitudes, perceptions, and behaviors; including measures to best predict future use of tobacco products other than conventional cigarettes (e.g., cigars, waterpipe, heated tobacco products, ENDS);
• Innovative measures, methods, or study designs to assess the likely impact of ENDS and heated tobacco products, other novel products, and/or potential modified risk tobacco products on relevant outcomes, including precursors to tobacco use (e.g., perceptions, intentions, susceptibility), and tobacco use behaviors including experimentation, initiation, progression, dual/poly use, complete switching, and cessation-related behaviors.

Communications - Understanding how to effectively communicate to the public regarding nicotine and the health effects of tobacco products through media campaigns and digital media. Priorities include:

• Identifying effective tobacco education messages, message components, and communication channels to prevent initiation and to counter uptake of ENDS use and other novel product use by youth and young adults;
• Developing methods to measure and track attention to tobacco education messages delivered on digital channels;
• Developing strategies to increase attention to and engagement with tobacco education messages delivered on digital channels;
• Identifying messages to effectively communicate about the risks associated with nicotine use and the potential relative harms of tobacco products other than conventional cigarettes use;
• Developing methods and messages for communicating complex scientific concepts to the general public, including information about the relative risks and harms of tobacco use (e.g., continuum of harm/harm reduction) while assessing and minimizing unintended consequences of such messages;
• Evaluating the effectiveness of text and pictorial warnings for tobacco products other than conventional cigarettes;
• Developing effective messages and communication for educating consumers about the health effects of cigars, waterpipe, heated tobacco products, ENDS, and novel tobacco products; and their relative harms as compared to cigarettes.

Marketing Influences Understanding the impact of marketing on susceptibility to and initiation of using tobacco products (both classes of products and products within classes) and transitions between experimentation, initiation, regular use, product switching, dual use, and cessation-related behaviors among different populations. Topics may include marketing such as advertising, digital media, and promotions. Priorities include:

• Methods, measures, and study designs to best assess the impact of tobacco product marketing (advertising and promotion) restrictions on users and non-users of tobacco with attention to vulnerable populations (if appropriate), including marketing of new/novel tobacco products;
• Understanding what components of ENDS marketing have the greatest impact on youth and young adults ENDS knowledge, attitudes, perceptions, beliefs, and behaviors;
• Understanding how labeling, marketing and advertising impact abuse liability, appeal, perceptions, and intentions to use different tobacco products;
• Examining the impact of potential marketing restrictions of new/novel tobacco products on various initiation and use behaviors (e.g., experimentation, initiation, use, and cessation) across developmental age groups (e.g., youth, young adult, non-user), as well as on adult continued use, dual use, switching, and cessation;
• Examining the impact of exposure to digital tobacco marketing on youth tobacco initiation and sustained use, including prevalence and frequency of exposure on different digital channels and the impact of social media influencers and other marketing partners (e.g., musicians).

Impact Analysis Understanding the potential or actual impact of FDA regulatory actions. Priorities include:

• Evaluation of local, state, federal, and international policies that are relevant to FDA CTP regulatory authorities (e.g., flavor bans, specific constituent changes or bans, minimum legal sales age, FDA-required cigarette health warnings), with a focus on effects on tobacco use/behavioral outcomes, including tobacco initiation and increasing use among youth and young adults, cigarette cessation and product switching among users, and prevalence change in vulnerable populations; as well as unintended consequences;
• Evaluation of tobacco product marketing authorizations of new/novel products (e.g., PMTA, MRTPA), such as potential impact on health outcomes and effects on tobacco use/behavioral outcomes, including patterns of use among users (e.g., dual use vs. switching) and initiation among unintended users (e.g., use by youth);
• Behavioral economics experiments and population-based modeling studies to estimate the range of potential impacts on behavior and health of potential FDA regulatory actions such as product standards addressing toxicity, appeal, and addiction (e.g., such as a ban on flavored cigars, a ban on menthol in cigarettes and cigars, lowering nicotine in combustible cigarettes, and ban on flavors that appeal to youth in any tobacco product);
• Evaluations of the differential impact and/or possible unintended consequences of tobacco regulatory actions among specific populations and, as appropriate, addressing how such actions may affect vulnerable populations;
• Health risk analysis at the population level to estimate the potential public health impacts of FDA regulatory actions such as tobacco product marketing authorizations of new/novel products (e.g., PMTA).

**The term "characteristic" encompasses materials, ingredients (including additives, nicotine formulations, and flavors), design, composition, heating source, and other features of a tobacco product, including harmful and potentially harmful constituents. Product characteristics can be incorporated into all the above topics.

Non-Responsive Research

Although the following research topics may be within FDA CTP’s regulatory authorities to fund, they are not to be included in the FOA and will be deemed non-responsive:

• Studies of short-term health effects and/or acute topography/clinical pharmacology testing of early generation ENDS products
• Mechanistic studies (i.e., basic science of disease development) unless biomarkers of harm with predictive value for disease development associated with tobacco product use is an outcome
• Studies developing or testing graphic health warnings for cigarette packages and advertisements
• Communicating harmful and potentially harmful constituents to the public
• Impacts of marketing restrictions on adults except for studies on newly authorized products
• Descriptive studies of demographics and/or risk perceptions that describe only exposure to advertising without linking exposure to tobacco use behaviors
• Studies of retailer compliance to the tobacco product regulations not associated with user behaviors or marketing strategies
• Studies of physician or other health professional knowledge, attitudes, perception, and behaviors toward the use of ENDS or other tobacco products

Applications that are incomplete and/or non-responsive will not be reviewed. As such, investigators are strongly encouraged to discuss whether their application is responsive to this FOA with a Scientific/Research Contact, listed in Section VII, prior to submission of their application. Additional information, including research priorities and a Frequently Asked Questions document can be found at: https://prevention.nih.gov/sites/default/files/2021-05/GeneralResponsiveness-FAQs_508.pdf

Part B. Administrative Structure Requirements

Each TCORS must have, at minimum, three Research Projects, an Administrative Core, and a Career Enhancement Core. At least three Research Projects and the Administrative and Career Enhancement Cores must be active at all times. Competitive applications will reflect more than an interesting collection of components; there must be evidence of the potential for a meaningful TCORS with an Integrative Theme and identity. The Center and its components should result in the generation of new knowledge in tobacco regulatory science. Coordination, communication, and when appropriate, collaboration is expected across the components of each TCORS, as well as across the TCORS program.

A program goal is improving the yield and impact of the tobacco regulatory science portfolio through enhanced capacity for sharing and comparing data, replicating findings, and integration of data from multiple sources. As such, use of common study variables, criteria, and protocols, where appropriate, is strongly encouraged. After awards are made, investigators will be expected to collaborate with other awardees, a designated Coordinating Center, a Center for Rapid Surveillance of Tobacco (CRST), and NIH and FDA CTP scientific staff on the development and use of shared and standardized measures, methods, and data management wherever feasible to facilitate data aggregation and collaborative activities across projects. As such, investigators are expected to incorporate PhenX measures, other common data elements, and/or standard measures recommended by TRS working groups as appropriate.

NIH and FDA encourage investigators involved in human-subjects studies to consider 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 available in PhenX Toolkit, including the Tobacco Regulatory Research Core and Specialty Collections. Please see NOT-OD-17-034 for further details.

TCORS will be required to cooperate with a designated Coordinating Center (CASEL), a Center for Rapid Surveillance of Tobacco (CRST), and federal partners to foster collaborations and cross-site scientific working groups to identify and address overarching conceptual and methodological issues.

A Steering Committee will be the governing body for all awardees funded under this FOA. The TCORS Steering Committee will include a principal investigator from each TCORS, a Coordinating Center (CASEL) principal investigator with tobacco science expertise, and NIH and FDA representatives. A non-voting member with logistical/administrative expertise from the Coordinating Center will also be included.

Research Projects

A proposed Center application must include a minimum of three fully developed hypothesis-driven Research Projects that contribute individually to the goals of the larger TCORS program and collectively to the Integrative Theme. Each Research Project must address one or more of the eight Scientific Domains, as defined above (Section I., Part A, Research Objectives Requirements): Product Composition and Design, Toxicity, Addiction, Health Effects, Behavior, Communications, Marketing Influences, and/or Impact Analysis. The Research Projects in the Center application must collectively address no fewer than two of the Scientific Domains. Applications that choose fewer than two Scientific Domains will be deemed non-responsive.

Each proposed Research Project must provide a clear description of its major goals, objectives, and how it integrates with the other Research Projects and/or Center components. Each Research Project director should be a qualified investigator and will be responsible for the scientific direction and conduct of the individual Research Project. Each applicant team should demonstrate in-depth expertise in all relevant scientific aspects of the proposed research activities. A description of how the aims of the Research Project will aid in the development and/or evaluation of tobacco product regulations is strongly advised.

Administrative Core

TCORS are required to have an Administrative Core. The Administrative Core should promote an environment of communication and collaboration among investigators within the proposed TCORS, across the TCORS funded through this RFA, with the Coordinating Center (CASEL), with the Center for Rapid Surveillance of Tobacco (CRST), and the FDA and NIH staff. The Administrative Core must provide for central operations to coordinate, monitor and facilitate attainment of the proposed TCORS' objectives, including quality control and oversight mechanisms for ongoing projects.

Each TCORS should have an External Advisory Board (EAB) that is charged to provide appropriate and objective advice and evaluation, as needed, to the Center. Each TCORS will determine the structure, membership, and meeting frequency (at least once per year) of its EAB. Federal partners must be invited to participate in the meetings and given a minimum 90-day advance notice of the meeting dates. EAB meetings are expected to take place at the TCORS institutions to permit the staff investigators (e.g., core leads and project leads) to attend and present progress and plans for their projects and cores. Adequate time should be allotted for robust discussion between TCORS investigators and EAB members. Meeting format should include a closed session of the Board to articulate recommendations for advancing progress, followed by a final open session to review these with the PIs and Federal partners. It is expected that the EAB generate a report or summary of the TCORS progress and recommendations to be shared with PIs and Federal partners.

Career Enhancement Core

There is continued need for investigators who have the quality and breadth of experience necessary to conduct cutting-edge research related to the regulation of the manufacture, distribution, and marketing of tobacco products. As such, each TCORS application is required to have a Career Enhancement Core that will provide exposure to and experience in Tobacco Regulatory Science (TRS). This core should focus on research experiences and related activities that will enhance development of TRS expertise, including aiding students, fellows, scholars, New and Early-Stage Investigators, and investigators new to TRS on their path towards becoming independent TRS investigators. These activities should budget for dedicated pilot research studies, as well as travel to relevant conferences and to other TCORS for purposes of collaboration, learning and research opportunities. Note: All the activities proposed should be structured so that they not only benefit the development of TRS expertise for both students and investigators, but also support and contribute to the overarching research goals of the TCORS.

Career/research enhancement activities are expected to include supervised research pilot studies. The studies may either fall within the overall theme of the TCORS (i.e., connecting to TCORS Research Projects) or be conducted as inter-TCORS collaborative studies. All proposed pilot projects will require prior approval from NIH and FDA CTP to assess responsiveness to FDA CTP Tobacco Regulatory Authorities before any expenditure of funds and/or work on the pilot project is initiated.

A unique opportunity is afforded the TCORS program to create collegial and collaborative networks among the TCORS investigators. TCORS are expected to develop mechanisms for establishing these networks and for sharing resources for development of TRS expertise, including existing curricula/courses, research opportunities, and the expertise of established investigators.

Self-standing institutional training/education/career development programs are NOT appropriate for this core and must not be proposed. For example, TCORS cannot support institutional National Research Service Award (NRSA) programs, such as T32 training grants.

Other Cores

TCORS may propose additional Cores as needed and justified (e.g., data, biospecimens, statistical, etc.).

Special Considerations

Applicants should keep the following special considerations in mind as they prepare their applications:

• Data Harmonization for Tobacco Regulatory Research via the PhenX Toolkit: This kit provides Core and Specialty Collections for inclusion in human subjects research to enable sharing, comparing, and combining of data and results. Using common measures will also assist program assessment of scientific progress in the field, identification of new research opportunities, and formation of collaborations to promote discovery and to resolve areas of scientific controversy. The Coordinating Center will facilitate these collaborations amongst TCORS in conjunction with the NIH and the FDA CTP scientific, administrative, and program staff.
• Tobacco Industry Funding of Applicants: The FDA CTP has adopted the following guidance regarding tobacco industry funding of applicants responding to this RFA. The National Advisory Council on Drug Abuse (NACDA) has set forth points 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. This includes any consulting relationships (paid or unpaid) with the tobacco industry or organizations supported in whole or in part by this industry. Please see (https://www.drugabuse.gov/about-nida/advisory-boards-groups/national-advisory-council-drug-abuse-nacda/council-statements/points-to-consider-regarding-tobacco-industry-funding-nida) for details. While this guidance was originally issued for NIDA applicants, it is relevant for all applications submitted under this RFA.
• Recommended Guidelines for the Administration of Drugs to Human Subjects: NACDA also 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 https://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects

NOTE: Applicant institutions may submit multiple applications in response to this FOA, CRST and CASEL RFAs. The TCORS PD/PI awardee, however, cannot serve as PD/PI of a CRST awardee nor as key personnel of a CASEL awardee.

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 from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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, are 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.

• 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.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
• Dun and Bradstreet Universal Numbering System (DUNS) Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, after obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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

The Center PD(s)/PI(s) should be (an) expert(s) in tobacco research, with, at minimum, R01- equivalent research experience, and ideally with experience successfully leading large multi-disciplinary Research Projects. The PD(s)/PI(s) should make substantial time and effort commitments and demonstrate capability to coordinate/collaborate within the proposed Center (that is, across the Center components) and across the TCORS program (that is, among the Centers funded under this FOA, as well as a coordination center and NIH and FDA staff).

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.

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

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

Note: Applicant institutions may submit multiple applications in response to this FOA, RFA-OD-22-004 (TCORS), RFA-OD-22-003 (CASEL), and RFA-OD-22-002 (CRST) RFAs. The TCORS PD/PI awardee, however, cannot serve as PD/PI of a CRST awardee nor as key personnel of a CASEL awardee. Key personnel of a TCORS awardee cannot include key personnel from the research team of a CASEL awardee.

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Tobacco Regulatory Science Program
Office of Disease Prevention
Telephone: 301-451-7464
Email:[email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative Core)	6
Career Enhancement Core (use for Enhancement Core)	6
Center-Named Core(s) (use for Other Core(s))	6
Project (use for Research Projects)	12

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Career Enhancement Core: required
• Center-Named Core(s): optional
• Research Projects: a minimum of 3 required

When preparing your application, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions. The following additional guidance applies:

Project Summary/Abstract: The Project Summary/Abstract should include the overall goals for the TCORS and clearly state the Integrative Theme that unifies the center. Also include a description of the Research Projects and how they collectively address at least 2 of the Scientific Domains outlined in the Funding Opportunity Description.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

The TCORS PD/PI awardee cannot serve as PD/PI of a CRST awardee nor as key personnel of a CASEL awardee

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Describe the overall goals of the TCORS, including the integration of its components. Include a description of the Integrative Theme that focuses the TCORS, and make explicit the Scientific Domains that are addressed across the Research Projects. The Specific Aims page should also articulate how the TCORS and the Research Projects will inform the FDA's regulation of the manufacture, distribution, and marketing of tobacco products to protect public health.

Research Strategy: Describe the overall vision for the TCORS and explain the significance of the chosen Integrative Theme in relation to FDA's regulation of the manufacture, distribution, and marketing of tobacco products to protect public health. Describe the required components, that is, a minimum of three Research Projects, an Administrative Core, and a Career Enhancement Core, as well as any Center-named Cores that the TCORS elects to include. Describe how the components and each Research Project's goals and outcomes relate to the common unifying theme that integrates the TCORS. Describe the Scientific Domains that the Research Projects collectively address (a minimum of two Scientific Domains are required per TCORS), explicating which Scientific Domains are addressed by each Research Project. Describe how the chosen Scientific Domains play to the strengths of the research team.

It is incumbent upon investigators to justify their choice of thematic focus, articulate the gap areas, and indicate how the proposed TCORS will inform the Research Objectives identified in this FOA.

Letters of Support: Are highly encouraged. There should be convincing evidence of the applicant institution's commitment to the TCORS. For TCORS with involvement of multiple geographic sites, all institutions involved may wish to provide documentation of their commitment to the TCORS.

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

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

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions. Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The TCORS PD/PI awardee cannot serve as PD/PI of a CRST awardee nor as key personnel of a CASEL awardee

Budget forms appropriate for the specific component will be included in the application package.

U54 Center applicants must budget appropriate funds to support travel of investigators and appropriate Center staff to the NIH planned investigator meetings. Investigator meetings will be convened once a year throughout the project to consider, as appropriate, common data elements, cross-site projects. The meetings will also provide opportunities to assess scientific progress, highlight work of junior investigators and identify new research opportunities. For purposes of budget planning, a single 2-day meeting to be held in Washington, D.C. each year is anticipated, if circumstances allow for in-person meetings.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the Specific Aims of the Administrative Core, including the goals and strategies for managing and integrating the TCORS, and its components.

Research Strategy: The Administrative Core is expected to oversee the overall administration, coordination and management of the TCORS. Use sub-sections A-B defined below to describe the following elements:

Sub-Section A: Administrative Structure:

Articulate the process for management of the TCORS, including communication, coordination, and where appropriate, collaboration across the TCORS' Research Projects and Cores, Center for Coordination of Analysis, Science, Enhancement, and Logistics (CASEL), and with the Center for Rapid Surveillance of Tobacco (CRST). In instances where multiple geographic sites are involved, a clear plan for communications and research activities across the sites should be provided. Additionally, describe how the Administrative Core will facilitate communication and collaboration with other funded TCORS and NIH and FDA staff.

This must include the following components:

(a) an overall programmatic structure that effectively promotes scientific interactions within and across TCORS, provides for internal quality control of research and publications, and takes maximum advantage of the TCORS research capability (the description of these attributes is particularly important when there are multiple participating institutions in the TCORS);

At least a monthly TCORS meeting to provide center scientific and administrative updates in which PIs and Federal partners are able to participate;

(b) an administrative organization that has clear lines of authority, is managed efficiently and cost effectively, and enables effective use and leverage of resources;

(c) the use of an External Advisory Board (EAB) that is charged to provide appropriate and objective advice and evaluation, as needed, to the TCORS. Each TCORS should determine the structure, membership, and meeting frequency (at least once per year) of its EAB. Federal partners must be invited to participate in the meetings and given a minimum 90-day advance notice of the meeting dates. EAB meetings are expected to take place at the TCORS institutions to permit the staff investigators (core leads and project leads) to attend and present progress and plans for their projects and cores. Adequate time should be allotted for robust discussion between TCORS investigators and EAB members. Meeting format should include a closed session of the Board to articulate recommendations for advancing progress, followed by a final open session to review these with the PIs and Federal partners. It is expected that the EAB generate a report or summary of the TCORS progress and recommendations to be shared with PIs and Federal partners.

(d) an internal advisory, decision-making, and priority setting process to support the activities of the TCORS.

Letters of Support: Are highly encouraged. There should be convincing evidence of the applicant institution's commitment to the TCORS. For TCORS with involvement of multiple geographic sites all institutions involved may wish to provide documentation of their commitment to the TCORS.

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

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

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

When preparing your application, use Component Type Enhancement Core .

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used
• The TCORS PD/PI awardee cannot serve as PD/PI of a CRST awardee nor as key personnel of a CASEL awardee.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Provide the specific aims for the Career Enhancement Core that will facilitate and enhance the development of investigators' research expertise in Tobacco Regulatory Science.

Research Strategy: Describe how this Core will support research-related activities that will facilitate and enhance research expertise in Tobacco Regulatory Science, including aiding new and early career investigators on their path towards becoming independent investigators,

Address (at a minimum) the following aspects, explaining clearly how proposed research experiences and related activities will enhance development of TRS expertise of students, New and Early-Stage Investigators, and investigators new to TRSP:

• Plans for supervised research activities for students, New and Early-Stage investigators at the TCORS that will enhance their research capabilities in Tobacco Regulatory Science.
• Plans for career enhancement pilot projects should include the following:
• Justification for budgeting and how these pilot projects will provide investigators with exposure to and experience in Tobacco Regulatory Science;
• Explanation of how the pilot studies will be solicited/developed and screened within the TCORS for responsiveness to FDA CTP regulatory authorities. Once pilot studies are selected by the TCORS, they must be submitted to Federal partners for approval to ensure that they are within scope of FDA CTP regulatory authorities.

Other relevant strategies and activities to enhance research capabilities of students, New and Early- Stage investigators in tobacco regulatory science may also be described, especially those that may help these investigators obtain independent research funding to sustain their future research. Examples of such activities include acquiring specific scientific skills or generally needed skills (like grants writing skills, manuscript writing) for a research career incorporating Tobacco Regulatory Science. Applicants may propose potential rotations to other TCORS or other cross-TCORS collaborations to provide enhanced research experience and conduct collaborative pilot projects.

Note that all proposed pilot projects must be approved for responsiveness to FDA CTP regulatory authorities by NIH and FDA prior to implementation and any expenditure of funds.

Letters of Support: Are highly encouraged. There should be convincing evidence of the applicant institution’s commitment to the TCORS. For TCORS with involvement of multiple geographic sites all institutions involved may wish to provide documentation of their commitment to the TCORS.

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

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

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Enhancement Core)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

When preparing your application, use Component Type Center Named Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The TCORS PD/PI awardee cannot serve as PD/PI of a CRST awardee nor as key personnel of a CASEL awardee

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the specific aims of the additional Center-proposed Cores that may be a part of the TCORS. Each Center-proposed Core must have a separate specific aims page.

Research Strategy: Where justified, an application may propose shared technical, statistical and/or laboratory resources, creating a core for centralized management (e.g., data, biospecimens, etc.). A separate research strategy should be submitted for each Center-proposed core. The justification for the need of a core service or resource should be clearly stated, along with the scientific and technical merit of the proposed core. The function of the core and how it will serve the TCORS must be described clearly. The core director(s) must be appropriately trained, qualified and well suited for the core activities proposed and must commit sufficient time and effort.

Letters of Support: Are highly encouraged. There should be convincing evidence of the applicant institution’s commitment to the TCORS. For TCORS with involvement of multiple geographic sites all institutions involved may wish to provide documentation of their commitment to the TCORS.

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

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. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Center-Named Core(s))

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

When preparing your application, use Component Type Project.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question

Project Summary/Abstract: Provide a Project Summary/Abstract narrative for the proposed Research Project that includes the project goals, how it addresses the selected Integrative Theme of the TCORS, and which of the Scientific Domains are addressed by the project outcomes. Note: each Research Project must address at least 1 of the Scientific Domains outlined in the Funding Opportunity Description, whereas collectively the TCORS must address no fewer than 2 Scientific Domains.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Application guide states that Project Narrative is required. However it is only required for the Overall component. If you would like the applicant to provide a project narrative for this component, update the above instructions accordingly. Specific names provided for Other Attachments must be no more than 50 characters including spaces.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The TCORS PD/PI awardee cannot serve as PD/PI of a CRST awardee nor as key personnel of a CASEL awardee.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Delete if neither Resubmissions nor Revisions are allowed; modify if one or the other is allowed.

The most commonly referenced Research Plan attachments are listed below for your convenience. FOA specific instructions are required for the Specific Aims and the Research Strategy in each component. FOA-specific instructions are optional for Letters of Support. Delete Letters of Support if there are no FOA-specific instructions.

Specific Aims: Outline the Specific Aims of the proposed Research Project, including hypotheses. Explain how the Research Project fits into the overall Integrative Theme of the TCORS, and which Scientific Domain(s) it addresses. A description of how the Specific Aims will aid in the development and/or evaluation of tobacco product regulations is strongly advised.

Research Strategy: Use Sub-Sections A-D defined below to describe the Research Project. Explain clearly in relevant sub-sections how the project conforms to the general requirements outlined in Section I (Funding Opportunity Description), including its relevance to the overarching Integrative Theme, how it addresses at least one of the required Research Objectives, and any of the listed FDA research priorities that might be addressed. The Research Project should provide a clear description of its major goals, objectives, and how it integrates with the other Research Projects and/or Center components.

In addition to the standard items covered by applicable instructions in the SF424 (R&R) Application Guide, address the following aspects in sub-sections A-D:

Sub-Section A: Significance. Describe the central problem/hypothesis being addressed and the premise for the Research Project. Describe how the proposed outcomes will contribute to meeting the goals and objectives of the TCORS and its Integrative Theme. Indicate the Research Project's relevance to the Scientific Domain(s) being addressed, and any research objectives of the FDA CTP. Include a description of how the outcomes will improve scientific knowledge and/or technical capacity related to the manufacture, distribution, and marketing of tobacco products.

Sub-Section B: Rationale. Include any data and rationale supporting the proposed hypotheses and/or outcomes of the Research Project. Include any relevant original research preliminary data, including data that addresses feasibility, validity of models or methods, and/or rationale for the hypotheses being tested. Regardless of the availability of applicant-generated preliminary data, the concepts for the proposed projects must be well developed and rigorous. The Research Project is expected to be supported by a strong rationale that is based on integrating to the extent possible the available relevant information from various sources.

Sub-Section C: Innovation. Describe how the Research Project may challenge or seek to shift current research in the field of tobacco regulatory science. Include any refinements, improvements, or new applications of theoretical concepts, approaches or methodologies, or instrumentation proposed. Describe how the outcomes of the Research Project will provide new information to further develop the knowledge base that informs the manufacture, distribution, and marketing of tobacco products in order to protect public health.

Sub-Section D: Approach. Describe the specific strategies and methods that are being proposed, and explain the rationale for selecting the methods to accomplish the Specific Aims of the project. List the anticipated measures, referencing any proposed PhenX Toolkit measures and/or other standardized, validated, or consensus measures, common data elements that will be incorporated into data collection protocols where appropriate. Provide a justification for not including any measures from the PhenX Toolkit if none are proposed. Describe the research design, conceptual procedures, and analyses to be used. Discuss the potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims. As part of this section, provide a tentative sequence or timetable for the project.

Letters of Support: Are highly encouraged. There should be convincing evidence of the applicant institution's commitment to the TCORS. For TCORS with involvement of multiple geographic sites all institutions involved may wish to provide documentation of their commitment to the TCORS.

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

If not adding any modifications, replace the text above with the following modifications with . and delete the bullets below. If using either bullet 1 or bullet 2 as a modification, delete the bullet you are not using. DO NOT KEEP BOTH BULLETS.

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

Appendix:

If there are modifications to Appendix instructions, (see https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-129.html), add the following text:

", with the following modifications"

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions. Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Research Projects)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. 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) using ASSIST or other electronic submission systems. 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) 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.

Awards funded under this FOA are not subject to SNAP authorities and do not have authority for the carryover of unobligated balances from budget period to any subsequent budget period without prior written approval from NIH. Special reporting requirements also apply, as described in Section VI.3. Reporting.

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads 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) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by FDA and components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. Prior to submitting their application, applicants are strongly encouraged to discuss whether their research ideas are responsive to this FOA with a Scientific/Research Contact listed in Section VII, and to review Frequently Asked Questions associated with this FOA at http://prevention.nih.gov/tobacco.

In order to expedite review, applicants are requested to notify the Tobacco Regulatory Science Program by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

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

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 issue or a critical barrier in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge and/or technical capability be improved? How will successful completion of the aims affect the concepts, methods, and technologies related to the manufacture, distribution, and marketing of tobacco products?

In addition, for applications involving clinical trials

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

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

In addition, for applications involving clinical trials

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

Does the application challenge and seek to shift current research in the field of tobacco science as it relates to the manufacture, distribution, and marketing of tobacco products? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, or instrumentation proposed? Will the outcomes of the project provide new information to further develop the knowledge base that informs the manufacture, distribution, and marketing of tobacco products in order to protect public health?

In addition, for applications involving clinical trials

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

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

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

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

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

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

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 arrangements?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the TCORS 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.

The overall TCORS will be evaluated as an integrated research effort. The review will assess the level of merit of the TCORS as an integrated effort, including the following criteria:

Center Coordination and Synergy:

• Is the Integrative Theme of the proposed Center clearly evident across Research Projects?
• Are TCORS Scientific Domains clearly specified?
• Is there evidence of the proposed Center's coordination/collaboration across the TCORS components (Cores, Research Projects)?
• Are there advantages of conducting the proposed research as a center program rather than through separate research efforts? Will the research efforts taken together have more impact on the field than each separate project conducted in isolation? Will the research proposed in individual projects be enhanced by the Center?
• Are timelines and milestones in-place that will allow an evaluation of progress to be made?

Research Potential to Inform Regulatory Decision Making:

• Does the applicant clearly describe how Center Research Project outcomes and findings would inform potential regulatory decision-making?

Career Enhancement Plan:

• Can the proposed career enhancement core adequately provide the expertise, resources, and institutional commitment to students and investigators and move them towards independent careers in tobacco regulatory science? Have they provided adequate plans for networking and collaboration?

Study Timeline

Specific to applications involving clinical trials

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

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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

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

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

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.

Not Applicable.

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable.

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.

Not Applicable.

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 Center for Scientific Review 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 selection 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.

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

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

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

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 recipient’s business official.

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

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

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

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

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

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

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

Milestones: Future support of a study funded under this FOA is contingent upon adequate participant recruitment based on projected milestones.

Investigational Tobacco Products: Currently there are no federal regulations regarding clinical research involving the use of investigational tobacco products. The Draft Guidance on Use of Investigational Tobacco Products describes the Agency’s current thinking regarding the definition of investigational tobacco product and the kinds of information FDA intends to consider in making enforcement decisions regarding the use of investigational tobacco products until regulations are issued and become effective. In addition, FDA has provided information regarding research to be conducted using newly deemed tobacco products in the Guidance for Industry Investigational Use of Deemed Finished Tobacco Products that were on the U.S. Market on August 8, 2016, during the Deeming Compliance Periods.

Recipient-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation

• The recipient institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The recipient institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, and request NIH pre-approval of substantial protocol changes before implementation, consistent with NIH DSMP policies.

All pilot projects will require FDA CTP and NIH approval prior to initiation and expenditure of funds on the project. To request approval, the TCORS must submit a document with the following information to the U54 coordinating center (RFA-OD-22-003)

• TCORS Institution
• Title of Proposed Study
• Project PI and Co-PI
• Pilot Project PI Status (should be one of the following):
• Assistant Professor
• Associate Professor
• Professor
• Graduate student and name of supervisor(s)
• Post-doctoral trainee and name of supervisor(s)
• Other (please specify)
• Proposed Period of Study - include start and end dates
• Total Funds Requested

A narrative similar to the specific aims page in an NIH grant application that includes:

• A brief background of the project
• Specific aims, objectives, or hypotheses
• Significance and relevance of the proposed research to FDA CTP s regulatory
• authority

All pilot project research must remain within scope of the approved pilot proposal and FDA CTP regulatory authorities.

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

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

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

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

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

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. 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 https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• 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.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Defining objectives and approaches for individual research activities;
• Overseeing the planning and conducting of studies for their research projects, data analyses and interpretation;
• Ensuring the conducted research remains within the scope of the regulatory authority of the FDA CTP;
• Ensuring and overseeing timely results reporting, including preparation and publication of scientifically rigorous manuscripts and dissemination of relevant findings by other appropriate means to the broad public;
• Serving as voting members of the TCORS Steering Committee and participating in relevant subcommittees;
• Attending the annual Investigator meetings;
• Accepting and implementing priorities, procedures, and policies agreed upon by the TCORS Steering Committee to the extent consistent with applicable grant regulations;
• Overseeing the implementation for their respective research projects of the common processes and procedures approved by the TCORS Steering Committee;
• Informing the NIH Program Official of plans to change or modify any project’s specific aims or research strategy, and obtaining receipt of NIH and FDA approvals prior to the implementation of changes and expenditure of funds;
• Cooperating with the other PDs/PIs, and with Federal staff members in various joint activities; examples include: research collaborations and working groups;
• Coordinating, as needed, activities associated with individual research projects with those of an NIH-FDA designated Coordinating Center; and
• Cooperating with the Federal staff members and/or external evaluators in the course of an evaluation process.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

Designated NIH Tobacco Regulatory Science Program (TRSP) scientific staff, acting as a Project Coordinator, will have the following responsibilities reflecting substantial scientific-programmatic involvement:

• Serving as voting member of the TCORS Steering Committee;
• Providing technical assistance, advice, and coordination of efforts to recipients;
• Identifying and providing relevant content expertise on behalf of NIH and FDA to the individual research projects, and serving in a liaison role;
• Cooperating with the PDs/PIs to support the research and dissemination of findings of the individual projects;
• Serving as a liaison between the TCORS Steering Committee and NIH and FDA;
• Assisting the TCORS Steering Committee in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action;
• Reviewing (together with NIH and FDA program officials) the progress of each participating institution and compliance with the components to collaborative efforts; and
• Participating in trans-TCORS working groups and committees, as appropriate.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice

Designated NIH scientific staff, acting as the Project Collaborators, will have the following responsibilities reflecting substantial scientific-programmatic involvement:

• Reviewing the scientific progress of individual recipients;
• Reviewing the compliance of individual recipients with the operating policies developed by the TCORS Steering Committee;
• Notifying, as warranted, the TCORS Steering Committee and the appropriate NIH offices concerning failure of the research projects or the Coordinating Center to adhere to policies established by the TCORS Steering Committee;
• Providing advice and technical assistance regarding the conduct of research; and
• Participating in trans-TCORS working groups as appropriate

In instances where significant involvement in the design of studies and/or analysis of results has occurred, the IC Project Collaborator may cooperate with recipients as coauthor in preparing publications of data resulting from the research. In this regard, he/she will be subject to the publication/authorship policies governing all participants. In addition, publications involving IC staff require internal clearances

NIH reserves the right to recommend withholding support, suspension, or termination of a U54 award for lack of scientific progress, failure to adhere to policies established by the TCORS Steering Committee, or substantial breech to the Terms of the Award.

In addition, an NIH IC Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Designated Food and Drug Administration (FDA) Center for Tobacco Products (CTP) scientific staff, acting as Project Coordinator, will have the following responsibilities reflecting substantial scientific-programmatic involvement:

• Serving as voting member of the TCORS Steering Committee;
• Providing technical assistance, scientific input and coordination of efforts to recipients;
• Identifying and providing relevant content expertise to the individual research projects, as needed;
• Cooperating with the PDs/PIs to support the research and dissemination of findings of the individual projects;
• Assisting the TCORS Steering Committee in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action; and
• Reviewing (together with NIH program officials) the progress of each participating institution and compliance with the components to collaborative efforts.

The Government, via the NIH and FDA Project Coordinators, Project Collaborators and Program Officials, will have access to data generated under this Cooperative Agreement through grantee meetings and progress reports. Federal staff may use information obtained from the data for the preparation of internal reports on the activities of the study.

Areas of Joint Responsibility include:

TCORS Steering Committee

Roles. The TCORS Steering Committee will be the main governing body for this initiative and will provide input on scientific matters. The TCORS Steering Committee members will provide scientific and technical input into discussions of pooled and collaborative research projects where relevant.

The TCORS Steering Committee, in partnership with NIH and FDA members, will monitor the progress of these projects, facilitate common data sharing and group publications and identify common resources to support such efforts.

Composition. The TCORS Steering Committee for this initiative will consist of the following voting members:

• A representative of each U54 award who will have one vote for the U54 they represent;
• One representative of a Coordinating Center; and
• The TRSP Coordinator and one IC representative from each participating IC will each have one vote
• The FDA Coordinator who will have one vote for the FDA.

Co-chairs of the TCORS Steering Committee must be a U54 PI.

All recipients will be required to accept and implement policies approved by the TCORS Steering Committee to the extent of corresponding grant regulations.

NIH staff will maintain authority on all matters regarding funding or expenditure of funds.

Subcommittees. The TCORS Steering Committee may establish subcommittees or workgroups to provide input on specific matters as needed. The NIH and FDA Project Scientists/Coordinators will serve on subcommittees or task forces, as they deem appropriate. Subcommittees or task forces may also include other representatives from NIH or FDA as non-voting members of the TCORS Steering Committee. The TCORS Steering Committee may invite additional, non-voting scientific advisors to the meetings. NIH reserves the right to augment the scientific expertise of the TCORS Steering Committee as it deems necessary.

Meetings. The TCORS Steering Committee will meet in person at least once a year at locations selected by the TCORS Steering Committee in consultation with NIH and FDA as part of the annual Investigators Meetings. In addition, the TCORS Steering Committee will meet regularly by conference call. The PD/PI of the Coordinating Center, and the PD/PI, and a senior investigator from each center must attend every in-person meeting of the TCORS Steering Committee, and the PD/PI or a senior investigator from each center award must participate in all conference calls as appropriate. The TCORS Steering Committee may invite additional individuals to participate at the annual Investigators Meetings.

Dispute Resolution:

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

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

A Mid-Period Progress Report (MPPR) will be due every six (6) months following the project start date, as well as the annual progress report. Electronic copies should be sent to the Grants Management Specialist listed on the Notice of Grant Award. The scientific summary should be a maximum of two (2) pages.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR 200.301.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

Rachel Grana Mayne, PhD, MPH
National Cancer Institute (NCI)
Telephone: 240-276-5899
Email: [email protected]

Lisa Postow, PhD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: [email protected]

Heather Kimmel, PhD
National Institute of Drug Abuse (NIDA)
Telephone: 301-402-0036
Email: [email protected]

Fred Tyson, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-0176
Email: [email protected]

Mary Garcia-Cazarin, PhD
Office of Disease Prevention (ODP)
Telephone: 301-451-2937
Email: [email protected]

Center for Scientific Review (CSR)
Email: [email protected]

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]

Judy Sint
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-480-1307

Email: [email protected]

Amy Bucheimer
National Institute of Drug Abuse (NIDA)
Telephone: 301-827-6694
Email: [email protected]

Michelle Victalino
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3336
Email: [email protected]

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 and 2 CFR Part 200.