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 Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This notice of funding opportunity (NOFO) invites proposals for Research Projects to advance the science of scale-up and sustainment of lung cancer screening (LCS) for populations at high risk for lung cancer. Each Research Project will propose a trial to test implementation strategies to equitably and effectively scale-up and sustain the delivery of LCS to a large number of diverse clinical care delivery settings and populations at high risk for lung cancer, with an emphasis on populations experiencing health inequities.    

Key Terms for the NOFO 

For the purpose of this NOFO, we define these key terms as follows:

Implementation Strategies: Methods or techniques to enhance the adoption, implementation, and sustainability of a clinical program or practice. For the purpose of this RFA, the implementation strategies are intended to support equitable and sustained implementation of LCS at scale. 

Lung Cancer Screening (LCS): A complex, multi-step, sequential intervention aimed at early detection of lung cancer using low-dose computed tomography (LDCT), and consisting of several essential processes: 1) identifying eligible individuals at high risk for lung cancer, 2) engaging individuals in shared decision making (SDM) to determine if they wish to undergo screening, 3) offering tobacco use treatment (TUT) services for all individuals with current tobacco use, 4) ordering and conducting LDCT imaging examinations for those individuals who decide to undergo screening, 5) interpreting and reporting LDCT results, 6) managing normal and abnormal findings, 7) ensuring appropriate follow-up care, and 8) promoting retention and adherence to repeat annual LCS while an individual remains eligible. High-quality LCS requires completion of all of these processes, although individual component processes may be bundled or integrated in different ways. Furthermore, because LCS is a preference-sensitive intervention, SDM is a critically important component process that might result in individuals deciding not to proceed with LDCT screening based on their personal preferences and discussions with their healthcare provider. For such individuals, not all of the other essential component processes of LCS are applicable. The United States Preventive Services Task Force (USPSTF) recommends “annual screening for lung cancer with low-dose computed tomography (LDCT) in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery”.

Scale-up: Deliberate efforts to broaden the impact of evidence-based interventions to benefit more people in a greater number and broader set of locations and settings. For purposes of this RFA, we further specify that a total of at least 60 sites must be included as part of the trial. Sites are defined as settings in which the delivery of LCS can and/or should occur. Examples of sites may include (but are not limited to) primary care clinics, specialty care clinics, community cancer centers, and Federally Qualified Health Center (FQHC) clinics.

SUMMIT Initiative: The SUMMIT Initiative includes a collection of Research Projects focused on scaling-up and sustaining LCS (SUMMIT LCS; funded by this NOFO RFA-CA-25-090), a collection of Research Projects focused on scaling-up and sustaining TUT for cancer survivors (SUMMIT TUT; funded by NOFO RFA-CA-25-010), NCI scientific and programmatic staff, and collaborative activities across all trials. As part of the overall SUMMIT Initiative, all trials will be required to use a core set of common measures and data elements to allow hypothesis testing and comparisons across LCS trials, comparisons across TUT trials, and comparisons across both LCS and TUT trials. The SUMMIT Initiative will include the use of supportive and collaborative infrastructure, such as a Steering Committee, thematic work groups, and virtual and in-person meetings, to facilitate advancing the science of scale-up and sustainment in cancer prevention and control.  

Sustainment: Continued delivery of an evidence-based intervention after implementation is achieved to maximize impact on population health outcomes. For purposes of this RFA, we further specify that sustainment must be measured as an outcome at least 12 months after implementation is completed.

Tobacco Use Treatment (TUT) Services: Evidence-based interventions and approaches that promote and support an individual's transition from current use to abstinence from all tobacco products. Intervention approaches include (but are not limited to) ‘Ask, Advise, Assess, Assist, and Arrange’, ‘Ask, Advise, Refer’, and ‘Ask, Advise, Connect.’ Interventions include (but are not limited to) behavioral counseling, FDA-approved medication, Smokefree.gov, and SmokefreeTXT. 

Background

Lung Cancer Screening in the United States. Lung cancer is the leading cause of cancer death nationwide. LDCT screening for lung cancer is an evidence-based intervention with the potential to detect lung cancers early, when they are more easily treated, resulting in reduced mortality and morbidity, and improved survivorship and quality of life. In 2011, the NCI-sponsored National Lung Screening Trial (NLST) was the first randomized controlled trial to demonstrate the effectiveness of LCS with LDCT. The NLST found a 20% reduction in lung cancer mortality and a 7% reduction in all-cause mortality following an offer of 3 annual LDCT screens, in a group of participants aged 55-74 years with a 30 pack-year history of smoking and who were currently smoking or had quit within 15 years. This landmark study provided the key evidence used by both the USPSTF grade B recommendation in 2013, and the National Coverage Determination by CMS in 2015 guaranteeing Medicare’s LDCT screening coverage. More recently, in 2021, an updated USPSTF recommendation broadened the pool of screening-eligible individuals by lowering the pack-year requirement from 30 to 20 and also decreasing the screening start age from 55 to 50 years. Current USPSTF recommendations also specify that persons referred for LCS who currently smoke should receive smoking cessation interventions to prevent tobacco-caused disease. 

Despite these developments, uptake of high-quality LCS in the United States (U.S.) has remained low, with estimates ranging from 4.5-28% of eligible individuals. Estimates are lower for individuals from socioeconomically disadvantaged groups with disproportionately high lung cancer incidence and mortality who may benefit the most from LCS. The low uptake of LCS limits the potential positive impact of LCS on cancer outcomes and disparities, and calls for further research to identify barriers to implementing LCS, and effective strategies for overcoming these barriers and scaling-up high-quality LCS in diverse settings. Emerging data suggest the potential impact of such efforts: a recent analysis by Knudsen and colleagues shows that increasing uptake of LCS by 10%, including TUT with modest (15%) efficacy, could avert 309 cancer-specific deaths per 100,000 LCS eligible individuals, making LCS with tobacco use cessation one of the most effective means of achieving the goal of ending cancer as we know it. 

Components of LCS. High-quality LCS is a complex, multi-step, sequential intervention aimed at early detection of lung cancer using LDCT, and consisting of several essential processes: 1) identifying eligible individuals at high risk for lung cancer, 2) engaging individuals in SDM to determine if they wish to undergo screening, 3) offering tobacco use treatment (TUT) services for all individuals with current tobacco use, 4) ordering and conducting LDCT imaging examinations for those individuals who decide to undergo screening, 5) interpreting and reporting LDCT results, 6) managing normal and abnormal findings, 7) ensuring appropriate follow-up care, and 8) promoting retention and adherence to repeat annual LCS while an individual remains eligible. High-quality LCS requires completion of all of these processes, although individual component processes may be bundled or integrated in different ways. Furthermore, because LCS is a preference-sensitive intervention, SDM is a critically important component process that might result in individuals deciding not to proceed with LDCT screening based on their personal preferences and discussions with their healthcare provider. For such individuals, other essential component processes of LCS are not applicable. Different interventions and models for accomplishing these essential component processes of LCS have been developed in different settings (e.g., primary care practice, FQHC, integrated health system, cancer center), and these interventions and models vary in their approach and degree of centralization.

Challenges with Delivering LCS. The delivery of high-quality LCS is limited by numerous well-described barriers that operate at both the patient and provider level (e.g., low awareness of LDCT screening guidelines, difficulty in identifying eligible patients, lack of physician time, skills, and resources for engaging patients in SDM and TUT), and the organization level (e.g., inadequate clinical structures and processes for conducting high-quality LDCT screening and follow-up care; limited access to LDCT facilities).

Advancing the Science of Scale-up and Sustainment. Scale-up of evidence-based interventions is essential to reach all individuals, communities and populations who could benefit from receiving such interventions. Scaling-up interventions to a greater number and broader set of locations and settings is needed to maximize impact on health outcomes, but evidence for how best to do so is lacking. Case studies of such efforts exist but are largely in low- and middle-income countries, which may be less applicable to the health care and public health context in high-income countries, and the U.S. in particular. A few conceptual frameworks on scale-up exist that can help guide the process but are used in less than 25% of scale-up efforts. There is also evidence to suggest that the number and type of implementation strategies to scale-up interventions is likely to differ from those needed to implement interventions in more localized settings or smaller geographic regions. Evidence-based interventions must also be sustained to achieve long-term impact on population health. Sustainment is an integral part of the broader field of implementation science but, as with scale-up, is significantly understudied. Sustainment can be conceptualized as continued delivery of an evidence-based program after implementation is achieved. Although several frameworks outline key elements of sustainment, there are relatively few empirical studies of predictors of sustainment in cancer prevention and control, and still fewer on how to successfully achieve sustained delivery of effective interventions and services.

Specific Research Objectives and Requirements

Through this NOFO, NCI solicits applications that propose a Research Project to conduct a rigorous trial to identify effective implementation strategies for scaling-up and sustaining the delivery of LCS for populations at high-risk for lung cancer.

Applications must include the following: 

• Use of a randomized controlled trial design (e.g., parallel cluster randomized, stepped-wedge cluster randomized, and other types of randomized designs) to test implementation strategies to scale-up and sustain the delivery of LCS for populations at high risk for lung cancer; 
• A minimum of 60 sites, for which a single site may include (but is not limited to) a primary care clinic, specialty care clinic, community cancer center, FQHC clinic, and/or other contexts in which LCS is provided;
• A comprehensive focus on all essential component processes of LCS, ranging from identification of eligible patients to patient retention and adherence to repeat annual screening (see definitions);
• Measurement of the delivery of LCS services (offered and provided) at least 12 months after implementation is completed;
• Use of validated or established process and outcome measures, to support the transition to a core set of common measures and data elements developed in the SUMMIT Initiative;
• Sites that are diverse in size, location, and resources;
• Populations that are diverse in race, sex, ethnicity, geography, and socioeconomic status; and,
• Projects must include but need not be limited to populations experiencing health disparities and health inequities.

Applicants are further encouraged to consider the following when developing their Research Project: 

• Engagement and collaboration with key partners in all aspects of the Research Project. Examples of key partners include (but are not limited to) individuals or patients, health information technologists/EHR specialists, community advisory boards, clinical care providers, healthcare systems, professional associations, clinics, hospitals, NCI-Designated Cancer Centers, community cancer centers, community leaders, and others;
• Selection of primary, secondary, and exploratory outcomes that are of interest to key partners; 
• Operationalization, explanation, and justification of selection of sites, including efforts to minimize within or between site(s) contamination (where applicable); 
• Use of standardized, established methods for measuring and tracking adaptations to interventions and/or implementation strategies;
• Application of rigorous but pragmatic approaches and methods that enhance replicability; 
• Analyses to understand moderators, mediators, and/or mechanisms of implementation strategies to test (elements of) causal pathways for scale-up and sustainment of both/either implementation outcomes and/or health-related outcomes;
• Metrics on the pace of implementation strategies for scale-up and sustainment; 
• Inclusion of intervention and implementation strategy cost data for economic analyses, such as economic evaluations, cost-effectiveness, and micro-costing methods, among other types; and
• Potential for, and product(s) to support, generalizability of implementation strategies for scale-up and sustainment.

Applicants may consider leveraging existing infrastructure and networks of eligible sites for the scale-up and sustainment trial. Examples include networks of FQHCs, the Cancer Screening Research Network, Practice Based Research Networks, and the Cancer Prevention and Control Research Network.

UG3/UH3 Cooperative Agreement Award Mechanism
This NOFO will utilize a two-phase cooperative agreement (UG3/UH3) mechanism. Awards made under this NOFO will initially support a two-year maximum, milestone driven UG3 phase, with a possible transition to a four-year maximum UH3 phase. The UG3/UH3 application must be submitted as a single application following the instructions described in this NOFO. Milestones to be accomplished in the UG3 phase for transition to the UH3 phase must be proposed in the application. Only UG3 grants that have met milestones will be considered for transition to the UH3 phase. 

UG3 Phase
The UG3 phase of the application must describe all preparatory activities necessary for conducting the scale-up and sustainment trial during the UH3 phase. These preparatory activities include those related to (1) refining the implementation strategies for scale-up and sustainment of LCS and (2) revising and finalizing plans and processes necessary for conducting the scale-up and sustainment trial.

Specific activities for the UG3 phase include (but are not limited to):

• Refining and finalizing the implementation strategies for the scale-up and sustainment trial;
• Developing and refining data collection methods and measures, and transitioning to a core set of common measures and data elements developed in the SUMMIT Initiative;
• Updating power analyses and sample size estimates;
• Refining informed consent documents (where applicable);
• Demonstrating site commitment to participate in the trial;
• Finalizing design elements of the trial;
• Developing detailed plans and processes for data harmonization (using a core set of common measures to be developed by the SUMMIT Initiative) and data sharing in partnership with key collaborators and in accordance with NIH policies; 
• Pilot testing data pulls and data cleaning from EHR systems (where applicable);
• Engaging and collaborating with NCI scientific staff and other study teams as part of the overall SUMMIT Initiative; and
• Finalizing the trial protocol in preparation for submitting for IRB approval.

UG3 Phase to UH3 Phase Transition
Utilization of milestones is a key characteristic of this NOFO. A milestone is defined as a scheduled event in the project timeline signifying the completion of a major project stage or activity. Applications must include milestones for the UG3 phase that are objectively defined and quantifiable to ensure clear demonstration that the proposed milestones were met at the time of the transition request.

At the completion of the UG3 phase, the applicant will be required to submit a detailed transition request to the UH3 phase. An administrative review will be conducted by NCI program staff to decide whether a UG3 phase grant will be transitioned to a UH3 phase grant based on the following criteria:

• Successful achievement of defined milestones in the UG3 phase;
• Successful completion of all preparatory activities necessary for launching the scale-up and sustainment trial at the beginning of the UH3 phase;
• Potential for successful completion of the scale-up and sustainment trial during the UH3 phase;
• Availability of funds; and
• Programmatic priorities.

UH3 Phase
The UH3 phase of the application must include plans to conduct the randomized controlled trial to test the effect of implementation strategies on scaling-up and sustaining LCS. The application must contain detailed information about the proposed scale-up and sustainment trial.

Specific activities for the UH3 phase include:

• Conducting and completing all aspects of the scale-up and sustainment trial, from the initial IRB approval through final data analyses, study close-out, dissemination of study results, and data sharing; and
• Identifying whether the strategies had a statistically significant impact on increasing scale-up and sustained delivery of LCS for populations at high risk for lung cancer.

Continued funding during the UH3 phase will be dependent upon meeting annual UH3 milestones. It is expected that the trial will be completed within the UH3 grant period. The trial must meet all applicable NIH and Office for Human Research Protections (OHRP) policy requirements.

Non-Responsive Applications

The following types of activities remain outside the scope of this NOFO. Applications proposing them will be considered non-responsive to this NOFO and will not be reviewed.

• Applications that propose to test the efficacy of new, unproven cancer-related therapies, imaging, diagnostics, biologics, or devices (e.g., first-in-human studies or drug/device safety trials).
• Applications lacking milestones for the UG3 phase.
• Applications that do not propose to use a randomized controlled trial design.
• Applications that do not include at least 60 sites.
• Applications that do not propose to measure sustainment at least 12 months after implementation is completed.
• Applications that do not propose to scale-up and sustain all essential component processes of LCS.

Additional Information

Pre-application Information Session: Pre-application Information Session: NIH staff will hold a teleconference for potential applicants to answer questions related to this NOFO. Time, date, and dial-in information for the call will be announced at a later date in the NIH Guide Notice.

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

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status) of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance materials.

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 NOFO.

Section III. Eligibility Information

1. Eligible Applicants

All organizations administering an eligible parent award may apply for a supplement under this NOFO.

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 Government

• 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 Organizations) 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 not allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information. 

• 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 Grants.gov registration; 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 their 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. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations can only submit one application in response to this RFA

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - 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:

Cynthia A. Vinson, PhD, MPA
National Cancer Institute (NCI)
Telephone: 240-276-6745
Email:  [email protected] 

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

, with the following exceptions or additional requirements:

For this specific NOFO, the Research Strategy section is limited to 25 pages.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. 
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex (including gender identity, sexual orientation, or transgender status).
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex (including gender identity, sexual orientation, or transgender status).

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP guidance materials.

All instructions in the How to Apply - Application Guide must be followed.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

Travel Budget: Applicants must budget for travel expenses for three, 2-day in-person SUMMIT Initiative meetings: one in-person meeting during the UG3 phase and two in-person meetings during the UH3 phase. For each in-person meeting, applicants must plan for key personnel (e.g., PD[s]/PI[s]/MPIs, program manager/coordinator, and 1-2 other study investigators or key partners) to attend. Meetings will take place in the Bethesda, Maryland area. Other (non-budgeted) steering committee meetings will be held as teleconferences.

Publication Fees: Applicants must budget for publication costs for open access for published articles. In addition, applicants must budget for at least one publication resulting from collaborations across the SUMMIT Initiative. 

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Describe the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 phase and the UH3 phase. 

Research Strategy: Applicants should describe both the UG3 phase and the UH3 phase using the standard sub-sections of Research Strategy defined in more detail in the SF424 Application Guide with additional guidance below.

Sub-section A: Background and Significance

The applicant should include, address, or demonstrate the following:

• Explain the current context for LCS in the sites proposed in the trial and the significance of scaling-up and sustaining LCS in those settings; 
• Provide evidence that LCS is important to and a priority among sites where the trial would be conducted;
• Scientific expertise in relevant areas, including (but not limited to) implementation strategies, scale-up and sustainment, randomized controlled trial design, longitudinal and multilevel statistical analysis, engagement science, qualitative methods, mixed methods designs, and/or implementation theories, models, and frameworks;
• Scientific and practice expertise in LCS, populations at high risk for lung cancer, populations experiencing health disparities, diverse delivery contexts, TUT, clinical practice guidelines, SDM, and patient-centered care;
• History of successful cross-discipline collaboration, coordination, and communication; and
• Composition of scientific and practice teams that span type of expertise, diversity of perspectives, background, and stage of professional career, among other characteristics.
   

Sub-section B: Innovation: 

The applicant should address the following:

• Discuss how the proposed study fills a gap in the knowledge base of effective implementation strategies for scale-up and sustainment for LCS specifically and, ideally, for a broader range of multi-component, evidence-based cancer-related interventions. 

Sub-section C: Approach: 

This section should include a description of the approach needed to accomplish the objectives for the UG3 phase and the UH3 phase. The approach should be divided into the UG3 phase and the UH3 phase and address the following for each phase:

UG3 Phase: The UG3 part of the application must describe the proposed activities associated with preparing for the scale-up and sustainment trial in the UH3 phase. Specifically, the application should:

• Describe the proposed implementation strategies to be tested in the scale-up and sustainment trial;
• Provide preliminary quantitative and/or qualitative data that the proposed implementation strategies have the potential to significantly improve the scale-up and sustainment of LCS;
• Provide evidence that the proposed implementation strategies are appropriate for the population and setting, and comprehensive in addressing all essential component processes of LCS;
• Describe how the implementation strategies will be refined in preparation for the scale-up and sustainment trial;
• Describe activities related to revising and finalizing plans and processes in preparation for initiating the scale-up and sustainment trial at the beginning of the UH3 phase;
• Describe how health equity is incorporated into the content, focus, and components of all aspects of the study, including (but not limited to) trial design elements, selection of measures, partner engagement, priority populations, and refinement of implementation strategies; and
• Describe how relevant implementation theories, models, and/or frameworks have informed the overall proposed study, including (but not limited to) study hypotheses, selection and design of type of randomized controlled trial, selection of implementation strategies for scale-up and sustainment, process and outcome measures and statistical analyses.

UH3 Phase: The UH3 part of the application must describe the proposed scale-up and sustainment trial. Specifically, the application should:

• Describe plans for the proposed randomized controlled trial to test the effect of implementation strategies on the scale-up and sustainment of LCS for populations at high risk for lung cancer;
• Describe and justify the trial design elements;
• Justify the selection of the control or comparison condition and describe how changes that may occur within that condition will be measured over time;
• Identify, describe, and explain the selection and use of validated measures, including process and outcome measures for the primary outcome(s), secondary outcome(s), and exploratory outcomes, as applicable. Include the flexibility to transition to a core set of common measures developed in the SUMMIT Initiative;
• Describe how the trial will comprehensively target and measure the key component processes of LCS;
• Describe how the study will measure and promote SDM and the elicitation of patient values and preferences as part of the overall LCS care delivery process, including instances where patients decide not to undergo LCS;
• Describe how the study will measure and mitigate the potential occurrence of LCS that does not adhere to either clinical practice guidelines or accepted quality standards; and
• Without duplicating information provided in the PHS Human Subjects and Clinical Trials Information Form, provide information about and justification for the proposed statistical and analytic plans for the trial, including (but not limited to) power and sample size calculations (including oversampling estimates), effect size estimates, operationalization, explanation, and justification of selection of ‘site’ within the trial, analyses for hypothesis testing, statistical approaches for handling missing data, efforts to minimize potential contamination within or between sites (where applicable), and attrition. Applicants are encouraged to consult available resources for guidance when developing statistical and data analytic plans (e.g., NIH Pragmatic Trials Collaboratory Design chapters; NIH Research Methods Resources; NCI Cluster Randomized Designs in Cancer Care Delivery Research Short Course).

Applicants should address how they will adhere to the NIH Policy on Good Clinical Practice Training. This policy establishes the expectation that all NIH-funded investigators and staff who are involved in the conduct, oversight, or management of clinical trials should be trained in Good Clinical Practice.

Milestones and Timelines

A timeline is required for all phases of the Research Project (UG3/UH3). In addition, specific milestones are required for the UG3 phase and should be incorporated into the timeline. A milestone is defined as a scheduled event in the project timeline signifying the completion of a major project stage or activity. Milestones will be used to evaluate the application in peer review as well as in consideration of the awarded project for funding of non-competing award years.

The application must include a section of proposed milestones for the UG3 phase that are clearly specified, well-defined, quantifiable, scientifically justified, and include objective criteria to allow for assessment of progress and success. Applicants must delineate what they propose to achieve during the UG3 phase in order to prepare for and proceed to the UH3 phase pending administrative review of successful completion of UG3 milestones. The milestones must include a timeline, a discussion of the suitability of the milestones for assessing success in the UG3 phase, and a discussion of the implications of successful completion of these milestones for the proposed UH3 phase. Only UG3 grants that have met milestones will be considered for transition to the UH3 phase.

Letters of Support: Applications must include letters of support from key partners collaborating on the project. Key partners may include (but are not limited to) individuals or patients, health information technologists/EHR specialists, community advisory boards, clinical practitioners, healthcare systems, professional associations, clinics, hospitals, NCI-Designated Cancer Centers, community cancer centers, community leaders, and others.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide. 

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• 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.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

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 How to Apply - 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 How to Apply - 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 How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply - 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 NOFO 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 How to Apply - Application Guide.

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected]. 

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

Applications in response to this NOFO will include two phases: the UG3 phase and the UH3 phase. Milestones to be accomplished in the UG3 phase for transition to the UH3 phase must be proposed in the application and will require NCI administrative review and approval before the UH3 grant is awarded. Annual milestones for the UH3 phase should also be proposed in the application.

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

Overall Impact

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

As part of the overall impact score, reviewers should consider and indicate how the Plan to Enhance Diverse Perspectives affects the scientific merit of the project.

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

Specific to this NOFO:
How well does the application demonstrate that the proposed implementation strategies are likely to impact scale-up and sustainment of LCS? How well does the application provide an explanation and justification for why the proposed implementation strategies for scale-up and sustainment fill a gap in the evidence base? How well does the application demonstrate that the outcomes are important to key collaborators and decision makers (e.g., individuals or patients, practitioners, healthcare systems, communities, and/or others involved in delivering and/or receiving LCS)? 

Investigator(s)

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

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?

Specific to this NOFO:
How well does the application provide evidence that the investigative team has expertise in implementation strategies, randomized controlled trials, implementation theories, models, and frameworks, scale-up and sustainment, lung cancer and LCS, populations at high risk for lung cancer, and measurement of implementation outcomes and health-related outcomes (among other relevant scientific areas)? How well does the application describe the involvement and inclusion of key partners and decision makers as collaborators in the proposed research? How well do the research-practice teams involved in the project represent diverse team composition, scientific expertise, lived experience and professional or career stage? How well does the application provide evidence of research-practice collaboration and effective communication?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

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?

Specific to this NOFO:
How well does the application demonstrate that the proposed implementation strategies fill a gap in the evidence base about scale-up and sustainment? 

Approach

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

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?

Specific to this NOFO:
How well does the application describe the process for refining the implementation strategies for scale-up and sustainment and for finalizing plans and processes to conduct the scale-up and sustainment trial? How well does the application address all essential component processes of LCS?

In addition, for the Milestones Plan -- To what extent do the proposed milestones provide sufficient detail for the planned tasks? To what extent are the milestones clearly defined, feasible, and quantifiable with respect to the proposed activities within the proposed timeframe? How appropriate are the milestones for the UG3 phase and do they reflect the ability to conduct all preparatory activities necessary to launch the scale-up and sustainment trial at the beginning of the UH3 phase? 
 

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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?

Specific to this NOFO: 
Are the proposed collaborations sufficient to meet study objectives? How appropriate are the collaborative research-practice teams for the proposed study? Is there a documented track-record of collaboration with key partners? Are the proposed sites diverse with respect to size, location, and resources, and is the selection of sites well-justified?

Additional Review Criteria

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.

Study Timeline

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)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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.

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

Applications will be assigned to the NCI. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. 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, including the PEDP, as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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 must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website. 
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

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 (HHS) grant administration regulations at 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 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 NIH as defined below. 
 

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

The PD(s)/PI(s) of each award will have the primary authority and responsibility for the project as a whole, including determining research approaches, designing protocols, setting project milestones in consultation with NCI staff, ensuring scientific rigor, conducting specific studies, analysis and interpretation of research data, and preparation of publications.

Specific rights and responsibilities will include the following:

• Oversee the overall budget, activities, and performance of the project;
• Conduct the scientific research in the project, reporting progress and milestones or objectives to NCI staff, reporting results to the scientific community, and disseminating approaches, methods, models, and tools broadly;
• Participate in a cooperative, interactive, and collaborative manner with NCI staff, including those outlined below under “NIH Responsibilities”;
• Submit a detailed transition request from the UG3 phase to the UH3 phase, outlining UG3 progress and accomplishment of milestones, and detailed plans, budget, and annual milestones for the UH3 phase. Note that funding of the UG3 phase of the cooperative agreement does not guarantee support of the UH3 phase;
• Submit materials and updates to the NCI on study progress, accomplishments, and challenges as requested;
• Facilitate the public release and dissemination of results, data, and other products generated through this award in a timely manner. All PDs/PIs are expected to share data and resources generated through this award in accordance NIH sharing policies and the goals of the NOFO;
• Comply with OHRP and FDA regulations concerning the protection of human subjects;
• Assume responsibility and accountability to the applicant organization officials for the performance and proper conduct of the research and administrative functions supported under this NOFO in accordance with the terms and conditions of the award, as well as all pertinent laws, regulations, and policies; 
• Operate in accordance with processes and goals as delineated in the NOFO; and
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.
• Provide updates at least annually on progress in PEDP implementation. 

In addition to standard annual Research Performance Progress Report (RPPR) submissions, PDs/PIs may be expected to supply additional progress-related information to the NCI.

Primary Responsibilities of NIH Program Staff

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate in a centralized fashion the various activities of the recipients. 

Specific responsibilities of the NCI Project Scientist(s) will include (but are not limited to):

• Provide scientific input on refining the proposed implementation strategies (e.g., providing methodological and statistical expertise and guidance on finalizing plans and procedures in preparation for the scale-up and sustainment trial);
• Participate as a voting member of the SUMMIT Initiative Steering Committee, SUMMIT LCS Sub-Committee, and relevant SUMMIT working groups;
• Provide scientific input on the design elements of the scale-up and sustainment trial;
• Provide input on scientific milestones and decisions regarding their finalization;
• Assist recipients to broaden their interactions with other NCI and NIH programs to disseminate results and tools from the SUMMIT Initiative and take advantage of existing NIH/NCI resources and infrastructures;
• Promote Initiative-wide adoption of common measures, common data elements, and cross-Research Project analyses;
• Convene and provide support to the LCS Sub-Committee in sub-committee activities; and
• Contribute to scientific manuscripts (e.g., co-authorship) and other scientific and scholarly activities (e.g., conference presentations) resulting from the project.

Additionally, an NCI Program Director who is not the Project Scientist will act as the NCI Program Official responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the NCI will monitor and evaluate progress to meet the expectations set forth by Congress in the 21st Century Cures Act. NCI also reserves the right to modify the budget or duration of funding or to curtail an award in the event of: (a) substantive changes in the project not approved in advance, (b) use of funds for activities not within the scope of the specific aims, (c) failure to make sufficient progress toward the project milestones, including timely pre-publication deposition of data or reagents in accordance with approved Consortium Policies, (d) failing to comply with the terms and conditions of the award or establish necessary statutory, regulatory, policy approval required for conducting the project, or (e) ethical or conflict of interest issues.

SUMMIT Initiative Consultants and Infrastructure Support: As part of the SUMMIT Initiative, NCI program staff will involve other NIH-supported infrastructure to support the SUMMIT Initiative activities and goals. In particular, NCI intends to actively and formally engage members of the NIH Pragmatic Trials Collaboratory to provide administrative, scientific, and content expertise relevant to the SUMMIT Initiative. Particular projects, individuals, and/or consultants who may provide the most appropriate level of support and expertise will be identified by NCI Program Staff in consultation with the SUMMIT Initiative Steering Committee and the SUMMIT LCS Sub-Committee. Potential areas where additional expertise from the NIH Pragmatic Trials Collaboratory and/or external consultants may be sought to complement expertise among the SUMMIT Research Projects include study design, statistical analyses, electronic health record systems, and/or health system and partner engagement.  

Areas of Joint Responsibility

SUMMIT Initiative Steering Committee: The Steering Committee will be the main SUMMIT Initiative governing body. The Steering Committee will be composed of one representative (contact PD/PI for multi-PI award and PI for single PI award) from each awardee funded under RFA-CA-25-009 (SUMMIT LCS), one representative (contact PD/PI for multi-PI award and PI for single PI award) from each awardee funded under RFA-CA-25-010 (SUMMIT TUT), and the NCI. Each representative on the Steering Committee will serve as a single vote on SUMMIT Initiative issues, in instances where decisions around policies or procedures are required, as appropriate. 

Two PD(s)/PI(s), representing one Research Project from SUMMIT LCS and one Research Project from SUMMIT TUT, will be selected to serve as chairpersons of the Steering Committee starting at the first meeting of the Steering Committee following awards issuance. 

The SUMMIT Initiative Steering Committee will meet monthly by video conference and in-person at least three times over the duration of the entire SUMMIT Initiative. 

The main responsibilities of the SUMMIT Initiative Steering Committee will include the following:

• Address and coordinate aspects relevant to Research Projects of the SUMMIT Initiative;
• Review progress of the SUMMIT Initiative toward meeting the overall Initiative goals of advancing the science of scale-up and sustainment;
• Develop overall policies and processes applicable to all SUMMIT Initiative awardees;
• Coordinate, organize, and disseminate Initiative output to the broader cancer research and practice community, including (but not limited to) manuscripts and oral and poster presentations at professional societies and scholarly meetings;
• Ensure that the SUMMIT Initiative takes advantage of existing NCI and NIH resources and programs;
• Establish thematic working groups, special interest groups, or subcommittees to accomplish the goals of the SUMMIT Initiative; and
• Stimulate and coordinate communications among awardees (e.g., resolve logistical problems, discuss solutions to technical issues, and share ideas). 

SUMMIT LCS Sub-Committee: The SUMMIT LCS Sub-Committee will be composed of all SUMMIT LCS PIs/MPIs and the NCI Project Scientist(s). The SUMMIT LCS Sub-Committee will focus on scientific and administrative directions for SUMMIT LCS and integration of efforts across the LCS Research Projects. The LCS Sub-Committee is required to report to the SUMMIT Initiative Steering Committee on a regular basis.

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

3. Data Management and Sharing

Consistent with the 2023 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.

4. 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 Section 8.4.1 Reporting.  To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

• Recipients will provide updates at least annually on implementation of the PEDP.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

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: https://www.era.nih.gov/need-help (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]

Wynne E. Norton, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6875
Email: [email protected]

Cynthia A. Vinson, PhD, MPA
National Cancer Institute (NCI)
Telephone: 240-276-6745
Email: [email protected]  

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

Crystal Wolfrey
National Cancer Institute (NCI)
Office of Grants Administration
Telephone: 240-276-6277
Email: [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 2 CFR Part 200.