Part 1. Overview Information

Key Dates

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

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

No late applications will be accepted for this Funding Opportunity Announcement.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The overarching purpose of this Funding Opportunity Announcement (FOA) is to provide support for research to facilitate well planned clinical trials aimed at advancing the science of tobacco cessation among adolescents. Specifically, this FOA invites applications for Planning Grants (R34) to inform the planning, design, and initial development of adolescent tobacco cessation behavioral intervention studies, with an emphasis on the critical developmental risk period ranging from mid- to late adolescence (i.e., approximately 14-20 years old). Applications should propose clinical trial planning activities that are scientifically necessary to guide the design and conduct of a future clinical trial evaluating an adolescent tobacco cessation behavioral intervention. Projects supported by this FOA must be grounded in the adolescent developmental literature and draw on a well-established theoretical model of behavior change. Planning activities could include, but are not limited to, preliminary studies and/or data acquisition to address information gaps related to the study population, intervention approaches, and/or outcomes/endpoints; feasibility and pilot studies to assess intervention viability and/or trial design; and testing of recruitment, retention, and adherence strategies to increase participant engagement and scientific rigor.

This FOA uses the Planning Grant Program (R34). This FOA runs in parallel with an FOA of similar scientific scope, RFA-CA-22-043 which utilizes the Research Project Grant (R01) mechanism.

Background

Tobacco product use among adolescents is a critical public health concern. Although cigarette smoking among adolescents has declined substantially since the mid-1990s, the prevalence of other tobacco product use has increased during the same time period. Since 2014, electronic nicotine delivery systems (ENDS) have been the most common tobacco product used by youth. Patterns of adolescent tobacco use have become increasingly complex with the greater availability, marketing, and promotion of diverse types of tobacco products (e.g., ENDS, cigars, cigarillos, waterpipe, oral nicotine products). Multiple concurrent tobacco product use (often called dual or poly tobacco product use) is now common among adolescents, for example, concurrent use of ENDS with cigarettes, cigars and/or smokeless tobacco. Co-use of tobacco and cannabis is also common among adolescents, for example, the concurrent use of tobacco and cannabis/THC via vaping devices and co-administration of cannabis and tobacco in cigars (i.e., blunts ). Moreover, certain adolescent subpopulations bear a disproportionate burden of tobacco use. For example, tobacco product use is higher among lesbian, gay or bisexual adolescents compared to heterosexual adolescents, and among adolescents with mental health conditions, those experiencing homelessness, and those involved with the community welfare or juvenile justice systems. There are also disproportionate burdens by type of tobacco product. For example, cigar use is higher among black high school students than white high school students.

Adolescence is a dynamic period of cognitive and psychosocial development during which the prefrontal cortex is still developing. During this period, youth are establishing their identity and autonomy, and increasing skills related to self-regulation and cognitive control. The adolescent period is characterized by an increased focus on peer relationships, increased autonomy from parents/guardians, and social role transitions. It is also the period at which individuals are most at risk of initiation, escalation, and entrenchment of tobacco use. There is substantial heterogeneity in adolescents trajectories of tobacco use uptake and progression to tobacco dependence; some progress rapidly from early trial to daily use, some escalate gradually from low-level, intermittent use to more regular use over a period of several years, and some maintain a persistent pattern of non-daily, light use. Intervening with tobacco use during the adolescent years provides opportunities to disrupt escalation of and/or promote cessation of tobacco use before it solidifies into persistent and long-term use, with downstream adverse health consequences for the remainder of the life course.

According to 2020 National Youth Tobacco Survey data, about two-thirds of adolescent tobacco users are interested in quitting and a similar proportion report having made one or more quit attempts in the previous 12 months. However, there is a dearth of evidence on effective approaches, strategies and interventions to promote cessation among adolescents. Existing treatment paradigms and pharmacotherapies, which were developed for adult cigarette smokers, have shown limited success when adapted and applied to youth. Despite ongoing research efforts, few empirically validated tobacco cessation interventions currently exist to help adolescents quit using tobacco. Research to expand cessation treatment options in this population is urgently needed.

Research to expand cessation treatment options in this population is urgently needed. Specifically, there is a need for well-designed, adequately powered, randomized controlled trials of behavioral interventions for adolescents that consider the unique developmental and behavioral aspects of tobacco use in this population, including factors that might promote or hinder cessation. Particularly needed are studies of interventions to promote non-cigarette tobacco cessation (e.g., ENDS, cigars and smokeless tobacco), to promote cessation in the context of dual and poly tobacco use behavior, and studies of interventions tailored to subpopulations with elevated tobacco use rates (e.g., African American youth, Native American/Alaska Native youth, LGBTQ youth, and youth with mental health conditions).

Research efforts in this area would benefit from careful planning and preliminary data acquisition to fill information gaps, and to overcome challenges associated with conducting adolescent-focused tobacco cessation clinical trials. Investigators often lack critical information about the study population, appropriate intervention timing and content, feasibility/acceptability of intervention approaches, and recruitment/retention strategies necessary to guide the design and conduct of clinical trials. The heterogeneity of tobacco use behaviors among adolescents can present challenges for the timing, design, and delivery of interventions. More research is needed to understand how well-timed interventions can take advantage of windows of opportunity to interrupt progression or encourage quitting among adolescent tobacco users. Furthermore, designing cessation interventions in a rapidly changing tobacco product landscape is challenging because of the heterogeneity of products and devices, even within the same product class, each of which may be associated with different cues, behaviors, and use patterns.

There is also a need for research to enhance our knowledge of factors that support successful recruitment and retention of adolescents in cessation trials, and that address the practical challenges and ethical considerations related to the study population. Many young people who use tobacco products do not self-identify as a smoker or tobacco user, which presents challenges for recruiting youth into treatment studies. Youth may also have concerns about confidentiality, which can be a barrier to recruitment. From a developmental perspective, adolescents willingness and ability to engage in and adhere to treatment may be suboptimal. Adolescents may not want treatment, believe it is unnecessary and/or may not prioritize treatment over school, work, or other activities. Even for youth who are motivated to participate in treatment studies, there are often logistical challenges to participation due to youth not having control over their schedule or not having independent means of transportation. To build the evidence base in this area, there is a need for research on study designs and methods that improve recruitment, retention and engagement of adolescents in cessation intervention studies.

Research Objectives

This FOA is intended to support clinical trial planning activities necessary to complete a future full-scale clinical trial of an adolescent tobacco cessation behavioral intervention. The planning activities will depend on the type of intervention under study and its stage of development, but may include collection of pilot/feasibility data, testing of recruitment strategies, and refinement of study design and intervention content. Pilot/feasibility trials, if included, should be designed so that results will provide information of high utility to support decisions about further development of the intervention approach or study design.

Clinical trial planning efforts should be targeted to individuals in the mid- to late adolescent period (approximately ages 14-20 years). Applications may address an adolescent age that is slightly younger or older than this range, as long as the mid- to late adolescent period is included. This FOA is not intended to solicit applications of only late adolescents into young adulthood (18+ years old). Planning activities should consider the unique characteristics and needs of adolescent tobacco users (e.g., dynamic period of neurodevelopmental plasticity and change, immature self-regulatory skills, socioemotional development) when designing and testing cessation interventions. In addition, consideration should be given to the potential for neurobehavioral treatment targets to be different for adolescents relative to adults (e.g., interpersonal processes, stress reactivity, self-regulation, nicotine enhancement of non-drug rewards). Intervention approaches considered as part of these clinical trial planning efforts should a) promote cessation of one or more forms of tobacco use among adolescents with established tobacco dependence, or to b) disrupt escalation of tobacco use among recent initiates and those who are using tobacco at low frequency and intensity. Interventions should be grounded in a well-established theoretical model of behavior change and informed by developmental science.

Tobacco cessation intervention research that includes adolescent subgroups with elevated tobacco use rates, and/or explicitly considers the sociocultural characteristics and needs of a specific subgroup is encouraged. The planning period should include engagement with stakeholders, as appropriate. Active stakeholder engagement may entail the meaningful involvement of stakeholders relevant to the study, such as adolescents, members of the community, leaders of community-based organizations, clinicians, health care systems, and others. Stakeholder engagement during the planning phase should help shape the design of the study, such as recruitment and retention approaches and the inclusion of populations who are underrepresented in research, as appropriate.

Cessation interventions are needed for the broad range of tobacco products, with particular interest in interventions targeting the products most commonly used by adolescents: ENDS, cigarettes, and cigars/little cigars/cigarillos. Additionally, interventions and planning efforts should consider the changing patterns of adolescent tobacco use (e.g., dual and poly tobacco product use). Clinical trials may be planned for a broad range of settings that have the potential to reach adolescents (e.g., schools, communities, health care settings). Where possible, investigators are encouraged to utilize existing infrastructure, community resources, and service systems (public and private). When selecting the mode of intervention delivery, investigators are encouraged to consider its appeal and accessibility to adolescents.

Applications that aim to understand and leverage advances in digital and mobile technology to reach and engage adolescents in cessation treatment are encouraged. Inclusion of these technologies should include consideration of review by FDA for authorization as part of the path forward (e.g., at what stage the applicant will reach out to FDA for feedback). Applicants should consider the potential for future adoption, implementation, and sustainability of interventions, at all stages of intervention planning and development, as appropriate.

Interventions may include FDA approved smoking cessation pharmacotherapies as long as they are being studied in the context of a behavioral intervention that is appropriate for the study population.

Studies may address co-use of tobacco and cannabis products. Studies that include cannabis use endpoints (including cessation) should describe the relationship of cannabis use to tobacco use, and why addressing cannabis co-use is important for tobacco cessation. The tobacco cessation measures should be considered as primary endpoints in such a study.

Examples of relevant areas of research include but are not limited to:

• Test and refine theory-derived intervention targets (i.e., objective, quantifiable, reproducible measures of target engagement);
• Identify and test strategies to support successful recruitment and retention of adolescents in cessation trials, including strategies to address practical challenges and ethical considerations related to the study population, as well as developmental considerations related to adolescent participant engagement;
• Perform studies to adapt and/or refine existing tobacco cessation behavioral treatment paradigms to address new tobacco products and new use patterns among adolescents, and/or to ensure they are developmentally and culturally appropriate;

• Collect feasibility data to inform decisions related to intervention approaches, study design, and/or study endpoints;

• Determine the acceptability of the intervention to study participants;

• Adapt and test an intervention or outcome instrument for a population that differs from the population for which the instrument was originally designed (e.g., the original intervention or outcome instrument was developed for adults and the proposal is to adapt and test with adolescents);

• Develop and pilot test the effectiveness of cessation intervention training tools (e.g., school-based intervention protocols meant to be implemented by teachers and other school staff; peer-to-peer counseling trainings);

• Determine protocols to optimize and adequately measure adherence to an intervention; determine if the level of achieved adherence is adequate to test the intervention;

• Standardize and validate survey instruments;

• Develop methods for measuring intervention fidelity, especially those intended to be implemented, disseminated and scaled up to real world settings and delivered by non-research staff.

Non-Responsive Applications

Applications with the following attributes will be deemed non-responsive and will not be reviewed:

• Applications that are focused on a population other than adolescents
• Applications that only propose to write a protocol or manual, develop infrastructure, or implement an already fully designed trial
• Applications that propose purely observational or descriptive research focused on adolescent tobacco use
• Applications that do not target cessation explicitly (e.g., applications that target reduced tobacco product use or lower risk use are non-responsive)
• Clinical trial planning activities for studies that only test a smoking cessation pharmacotherapy without a primary behavioral intervention
• Studies that offer one tobacco product as a cessation aid for another tobacco product

Special Considerations

Annual in meetings: Recipients will be expected to participate in an annual investigators' meeting that may be hosted at NCI and/or on a rotating basis at a participating grantee’s institution. The meetings will provide a forum for presenting scientific findings from the funded studies and will facilitate interactions among the community of funded scientists. Applicants should budget for the Principal Investigator and one additional project personnel to attend the planned annual grantee meeting. Investigators will be expected to participate in grantee meeting planning and may also be asked to participate in committees that meet periodically in a virtual format.

Standardization and coordination: Investigators are strongly encouraged to consider using best common measures available based on scientific consensus for sociodemographic variables, and key predictors and cessation outcomes to the extent possible to promote the collection of comparable data across studies. Investigators may refer to the Institute of Medicine reports entitled Capturing Social and Behavioral Domains in Electronic Health Records, the PhenX Toolkit, and other consensus documents for relevant measures. Funded investigators will, to the extent possible, be expected to collaborate and report key common variables in a standardized manner. Investigators may also be asked to collaborate in the development of survey measures, approaches to recruitment, retention and engagement, and other areas of shared investigator interest.

Tobacco industry funding of applicants: 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 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

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

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government
• 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)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are 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. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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).

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Gina Tesauro, MSW
National Cancer Institute (NCI)
Telephone: 240-276-6786
Email: [email protected]

Page Limitations

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

Instructions for Application Submission

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

Other Plan(s):

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

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

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

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

Specific Aims

• The goals of the expected outcome(s) of planning should be concisely stated in the Specific Aims section including the goals of any planned pilot/ feasibility trial. The specific objectives of the future trial must be clearly and concisely presented, including a specification of the primary and major secondary endpoints to be measured. There should be a clear explanation of the importance of various endpoints.

Research Strategy

Significance

• A discussion of the significance of the problem being studied, the need for the future trial, and the potential impact of the results of the future trial.

• A description of how the proposed planning activities will lead to the timely and successful implementation of a future clinical trial.

Approach

• A concise description of the overall strategy, methodology, and analyses to be used to accomplish the planning goals and specific aims of any pilot/ feasibility trial.

• Details of any pilot/ feasibility clinical trial that will be conducted as part of the award and the metrics that would signify success.

• A description of the potential problems, alternative strategies, and benchmarks for the success of the planning period and future trial.

• A description of the plans to identify and engage relevant stakeholders, if applicable.

• A discussion of how the proposed activities address any major barriers to the timely and successful implementation of the future trial.

Letters of Support: Provide all appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, and other collaborators. Letters of support should also be provided from individuals or organizations that have been or will be involved in stakeholder engagement efforts.

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.

The following modifications also apply:

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

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

4. Submission Dates and Times

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). 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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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

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

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.

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

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.

2. Review and Selection Process

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

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

Applications may undergo a 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.

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 National Cancer Advisory Board. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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.6. 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: Recipient 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: Generaland 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.

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

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

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals 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 information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, 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, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. 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.
  
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws 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.

Not Applicable

Data Management and Sharing

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

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

3. Reporting

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 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 Part 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.

Section VII. Agency Contacts

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

Rachel Grana Mayne, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-5899
Email: [email protected]

Evan Sullivan Herrmann, PhD
National Institute on Drug Abuse (NIDA)
Phone: 301-443-1428
E-mail: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
Email:[email protected]

Amy Connolly
National Institute on Drug Abuse (NIDA)
Phone: (301) 827-4457
E-mail: [email protected]

Section VIII. Other Information

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

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.