Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title
Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) Centers (U54 Clinical Trial Not Allowed)
Activity Code

U54 Specialized Center--Cooperative Agreements

Announcement Type
New
Related Notices

  • July 20, 2021 - Notice of Pre-application Webinar for Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) - RFA-CA-21-038 and RFA-CA-21-039. See Notice NOT-CA-21-097.
  • Funding Opportunity Announcement (FOA) Number
    RFA-CA-21-038
    Companion Funding Opportunity
    RFA-CA-21-039 , U24 Resource-Related Research Project (Cooperative Agreements)
    Assistance Listing Number(s)
    93.394, 93.395
    Funding Opportunity Purpose

    The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) Centers (U54). The overall goal of the CAP-IT Program is to establish an agile and effective network infrastructure to undertake collaborative research focusing on precision cancer prevention and interception, with the overarching goal of discovering molecularly or immunologically targeted agents designed to prevent or intercept the oncogenic process in higher-risk populations. To achieve the Program's overarching goal, CAP-IT research objectives are:

    • To identify targets that can be potentially exploited for cancer preventive or interceptive interventions specifically in higher-risk populations, by collaborating with the NCI and other programs with a research focus on molecular profiling of established precursor/precancer, early cancer, and/or oncogenic signaling pathways. High-value tumor-driving molecular targets/pathways, immune targets, and tumor-specific/tumor-associated antigens, collectively referred to as "oncotargets" in this FOA, will be prioritized for the discovery of targeted interventions;
    • To functionally validate the critical roles of the high-value oncotargets in tumor initiation and/or progression to invasive cancer and select oncotargets suitable for targeted intervention strategies; and
    • To discover innovative targeted agents through in vitro and in vivo efficacy evaluation and advance promising efficacious agents to the NCI's existing R&D pipeline for further development.

    The CAP-IT network will be formed by up to three U54 Specialized Centers (this FOA) and one U24 Data and Resource Coordination Center (see companion RFA-CA-21-039).

    Key Dates

    Posted Date
    July 15, 2021
    Open Date (Earliest Submission Date)
    September 07, 2021
    Letter of Intent Due Date(s)

    30 days prior to the application due date

    Application Due Dates Review and Award Cycles
    New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
    October 07, 2021 Not Applicable Not Applicable March 2022 May 2022 July 2022

    All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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

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

    Expiration Date
    October 08, 2021
    Due Dates for E.O. 12372

    Not Applicable

    Required Application Instructions

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

    Table of Contents

    Part 2. Full Text of Announcement

    Section I. Funding Opportunity Description

    Purpose

    The purpose of this Funding Opportunity Announcement (FOA) is to solicit Applications for Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) Centers (U54). The overall goal of this FOA and the companion FOA (U24 CAP-IT Data and Resource Coordination Center (CAP-IT DRCC) (RFA-CA-21-039) is to establish an agile and effective network infrastructure to undertake collaborative research focusing on precision cancer prevention and interception, with the overarching goal of discovering molecularly or immunologically targeted agents designed to prevent or intercept the oncogenic process in specific higher-risk populations. In this FOA, cancer prevention means primary prevention of cancer before the oncogenic process begins, while cancer interception is defined as disruption of the oncogenic process during the precursor or precancer state or stage. Precision cancer prevention-interception refers to an approach employing cancer preventive-interceptive interventions individually tailored for different higher-risk populations such as those with hereditary cancer syndromes (HCS) and individuals diagnosed with high-grade precursor abnormalities that place individuals at higher risk of cancer e.g., precancer. To achieve the Program's overarching goal, CAP-IT research objectives are:

    • To identify targets that can be potentially exploited for cancer preventive or interceptive interventions specifically in higher-risk populations, by collaborating with the NCI and other programs with a research focus on molecular profiling of precancer, early cancer, and/or oncogenic signaling pathways. High-value tumor-driving molecular targets/pathways, immune targets, and tumor-specific/tumor-associated antigens, collectively referred to as "oncotargets" in this FOA, will be prioritized for the discovery of targeted interventions;
    • To functionally validate the critical roles of the high-value oncotargets in tumor initiation and/or progression to invasive cancer and select oncotargets suitable for targeted intervention strategies; and
    • To discover innovative targeted agents through in vitro and in vivo efficacy evaluation and advance promising efficacious agents to the NCI's existing R&D pipeline for further development.

    The CAP-IT network will be formed by up to three U54 Specialized Centers (this FOA) and one U24 Data and Resource Coordination Center (the companion FOA, RFA-CA-21-039) .

    Key Definitions for the Context of this FOA

    • Cancer prevention: Cancer prevention is defined as primary prevention of cancer before the oncogenic process begins.
    • Cancer interception: Cancer interception is defined as disruption of the oncogenic process during the precancer stage before the development of invasive cancer.
    • Higher-risk populations, higher-risk cohorts: These are individuals with an increased risk of cancer such as those with hereditary cancer syndromes (HCS) and precursor abnormalities that place individuals at higher risk of cancer e.g., precancer.
    • Precision cancer prevention and interception: Precision cancer prevention-interception refers to an approach employing cancer preventive-interceptive interventions individually tailored for different higher-risk populations as defined above.
    • Oncotargets: Tumor-driving molecular targets/pathways, immune targets, and tumor-specific/tumor-associated antigens are collectively referred to as oncotargets in this FOA.
    • Actionable oncotargets: These represent previously identified and well-characterized targets as drivers or enhancers of oncogenesis, against which efficacious agents are already available for clinical studies but have not been explored for cancer prevention and interception.
    • Potentially exploitable oncotargets: These represent targets that are considered as potential drivers or enhancers of oncogenesis, detected in tumor precursor cells or in tumor stroma, which consists of immune cells, fibroblasts and other stromal components, and are prioritized based on the extent of expression, cell-type specificity (e.g. precancerous cells, tumor stromal components, and normal cells), types (i.e. mutated vs. wild type proteins), cellular expression patterns, timing (e.g. expressed early in oncogenesis), and prevalence of target expression among a defined higher-risk cohort.

    Background

    While much progress has been made in the development of new or improved methods of determining cancer risk and detecting and monitoring emerging precancer, current approaches for cancer risk reduction are still centered on surgical procedures. With the increasing knowledge of early drivers of the oncogenic process, reduction in cancer mortality can be significantly improved if oncogenic pathway-targeted interventions are successfully deployed to further mitigate cancer risk and better manage precancer especially in higher-risk populations. Because higher-risk populations represent a diverse group of individuals with different genetic susceptibilities, varying histories of exposure to carcinogens, different lifestyles, age, gender, and the presence of other comorbidities, it is nearly impossible to find and deliver universally efficacious cancer preventive interventions in this heterogenous population. A more rational approach to cancer prevention and interception in higher-risk cohorts is to employ preventive measures specifically tailored for individual risk factors, an approach referred to as precision cancer prevention-interception. Success of precision cancer prevention-interception depends on two complementary steps. First, higher-risk individuals need to be identified, e.g., through screening and early detection of precursor/precancers, some of which may progress to cancer, and testing for genetic susceptibility. Second, innovative, safe, and efficacious measures designed to reduce cancer risk or molecularly/immunologically intercept, arrest, and possibly eliminate precancer in these higher-risk individuals are needed to complement or replace surgical resection or ablation. However, because very few target-specific agents are available for these higher-risk individuals, current cancer interception strategies predominantly rely on surgical interventions. It is this gap in discovering and bringing risk-tailored targeted agents to the higher-risk populations for cancer prevention and interception that CAP-IT will address.

    Beginning with the earliest stage of tumor formation through the establishment of fully invasive cancers, oncogenesis is a continuum of dynamic interplay between emerging aberrant cell clones and the host tumor surveillance machineries. Better understanding of the early oncogenic processes and surveillance machineries can shed light on molecular physiological changes that are responsible for driving progressive tumor growth and weakening the host defense mechanisms. Recent advances in cancer immunotherapy with immune checkpoint inhibitors have indicated that the host’s own defense system can indeed mount effective antitumor immune responses if the tumor-associated immunosuppressive microenvironment is overcome by immune checkpoint blockade. Importantly, growth and progression trajectories of screen-detected and incidentally identified precancers are not uniform or linear. Biological and molecular events and changes in tumor precursor cells as well as in the tissue microenvironment can potentially tilt the balance for or against tumor growth. Some of these events may serve as oncotargets that can be exploited.

    The Human Tumor Atlas Network (HTAN) includes the Pre-Cancer Atlas (PCA), which specifically aims to: 1) construct comprehensive, dynamic, high-resolution, multidimensional, multiparametric, temporal and scalable atlases of precancer and their surrounding microenvironment and 2) more deeply understand the transition from pre-malignant to malignant state as a function of time, so better risk stratification and effective early intervention strategies can be developed. In addition to PCA, there are existing NCI programs with accessible genomic and molecular profiles and biomarker databases, including NCI Consortium of Molecular and Cellular Characterization of Screen-detected Lesions (MCL), the Cancer Genome Atlas (TCGA; through NCI Genomic Data Commons, GDC), NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Cancer Target Discovery and Development (CTD2). Furthermore, Early Detection Research Network (EDRN) and other biomarker discovery and translational research initiatives continually uncover oncogenic driver pathways and networks, some of which can be targeted to prevent or intercept the oncogenic process. CAP-IT is intended to take advantage of these existing program databases that can reveal potentially exploitable oncotargets and critical oncogenic modules for new agent discovery research.

    In targeted agent discovery, it is a prerequisite that viable and high-value targets be first functionally validated for their critical roles in the disease process, such as oncotargets for oncogenesis. Oncotargets validated and prioritized for agent discovery research may include actionable targets and those that are new but deemed potentially exploitable for interventions. Actionable targets represent previously identified and well-characterized targets as drivers or enhancers of oncogenesis, against which efficacious agents are already available for clinical studies but have not been tested for cancer prevention and interception. These agents include FDA approved or clinically investigated agents. Potentially exploitable targets represent those that are considered as potential drivers or enhancers of oncogenesis; detected in tumor precursor cells or in tumor stroma, which consists of immune cells, fibroblasts and other stromal components; and can be prioritized based on the extent of expression, cell-type specificity (e.g. precancerous cells, tumor stromal components, and normal cells), types (i.e. mutated vs. wild type proteins), cellular expression patterns, timing (e.g. expressed early in oncogenesis), and prevalence of target expression among a defined higher-risk cohort.

    One example of a successful outcome of molecularly targeted cancer preventive-interceptive intervention is the inhibition of hedgehog (HH) pathway in individuals with Gorlin syndrome. This autosomal-dominant cancer predisposition syndrome is caused by germline mutations in the tumor suppressor gene Patched-1 (PTCH1), which result in the aberrantly activated HH signaling and drive the growth of basal cell carcinomas (BCCs) of the skin. Use of a topical HH inhibitor has been shown to reduce BCC burden as well as to prevent new BCC growth in the affected individuals (J Clin Oncol 2018, 36: e21626). Other examples of potentially exploitable oncotargets that have been reported in the literature include DCLK1 for pancreatic precancer (Cell Stem Cell 2016, 18:441), OXPHOS pathway for lung precancer (Clin Cancer Res 2017, 23: 5091), frameshift mutation-derived neoepitopes in Lynch syndrome (Nat Comm 2020, 11:4740), progression-associated mutation-derived neoepitopes in lung adenomatous precancer (Cancer Res 2019, 79:5022), and WNT/CTNNB1 signaling pathway in familial adenomatous polyposis .

    CAP-IT establishes a new discovery research paradigm in cancer prevention that leverages the potential oncotarget leads identified from precancer biology research and related databases and exploits their oncogenic characteristics and vulnerabilities to discover innovative cancer prevention-interception agents especially focusing on higher-risk populations. The ultimate goals of CAP-IT are to advance newly discovered efficacious cancer preventive or interceptive agents to the existing NCI, Division of Cancer Prevention preclinical and clinical development pipelines, PREVENT Program for further development towards IND and Cancer Prevention Clinical Trials Network (CP-CTNet) for early phase clinical trials, and thereby to establish a scientific roadmap and a more streamlined foundational infrastructure for fast-tracking agent discovery and development for cancer prevention and interception from bench to bedside.

    Research Objectives and Key Requirements of the CAP-IT Centers

    To achieve the Program's overarching goal which is to discover molecularly or immunologically targeted agents designed to prevent or intercept the oncogenic process for precision cancer prevention and interception, CAP-IT research objectives are as follows:

    • To identify targets that can be potentially exploited for cancer preventive or interceptive interventions specifically in higher-risk populations, by collaborating with the NCI and other programs with a research focus on molecular profiling of precancer, early cancer, and/or oncogenic signaling pathways, and prioritize high-value oncotargets (see the definition above) for the discovery of targeted interventions;
    • To functionally validate the critical roles of the high-value oncotargets in tumor initiation and/or progression to invasive cancer and select oncotargets suitable for targeted intervention strategies; and
    • To discover innovative targeted agents through in vitro and in vivo efficacy evaluation and advance promising efficacious agents to the NCI's existing R&D pipeline for further development.

    (A) Required Center Capabilities. To maximize the potential of team science efforts, each CAP-IT Center (U54) may combine/integrate capabilities from a multi-institutional/multi-laboratory arrangement in order to undertake multi-disciplinary research involving the following three (3) major focus areas: target validation, screening and identification of active agents or antigenic epitopes, and in vivo efficacy testing. Each U54 CAP-IT Center may choose to focus its agent discovery research either on molecularly targeted, immunologically targeted interventions, or both. Accordingly, all proposed U54 CAP-IT Centers must have necessary scientific expertise, technical capabilities/skills, and infrastructure to carry out the expected scope of activities, including but not limited to the areas of investigation as listed below, through the formation of CAP-IT Center subunit(s) specialized in any combination of the 3 focus areas (see above) and a separate Administrative Core (for additional details on the requirements, please see Section IV Application and Submission Information):

    • Identify targets that can be potentially exploited for cancer preventive or interceptive interventions especially in higher-risk populations through collaborations with the NCI and other programs with a research focus on molecular profiling of precancer, early cancer, and/or oncogenic signaling pathways, and prioritize high-value oncotargets;
    • Validate the critical roles of the novel or less well-characterized intervention oncotargets in the early phase of tumorigenesis through functional evaluation studies (e.g., loss-of-function/gain-of-function analyses and synthetic lethality interaction studies);
    • Conduct informatic analyses of validated oncotargets for actionability, druggability, and/or feasibility of immune-targetability for cancer prevention and/or interception;
    • For molecularly targeted interventions, prioritize the validated oncotargets based on multiple factors, including but not limited to whether oncotargets are predicted to be susceptible to functional modulations; whether drugs or drug-like inhibitors are already available; whether druggable active sites are known; what role(s), if any, they may play in a normal physiological setting; whether pertinent structural biology data are available to help advance rational drug design/development; and whether screening assays for drug discovery are readily available or feasible;
    • For immunologically targeted interventions, evaluate the feasibility and appropriateness of immunological targeting approaches based on various factors, including but not limited to target antigen characteristics, sequence homology among different species (e.g. human and mouse), discoverability of potent T-cell epitopes, TCR affinity and avidity, and MHC class-I and MHC class-II binding predictions, and immunogenicity of antigens that may be expressed/delivered as peptides, recombinant proteins, and/or as nucleic acids (mRNA or DNA);
    • Confirm expression of the prioritized candidate oncotargets in pertinent preclinical models that recapitulate human cancer development, including the transition from precancer to cancer;
    • For molecularly targeted interventions, conduct in silico and in vitro screening for active compounds, using focused chemical libraries with well-characterized compounds for potency screening, such as FDA-approved drug library, NIH Clinical Collection libraries, and appropriate oncotarget or signaling pathway-specific libraries of drug-like small molecules with validated biological activities (Note: High-throughput screening of large compound libraries and iterative chemical optimization for lead compound identification are outside the scope of the expected activities in this FOA);
    • For molecularly targeted interventions, select and prioritize active compounds or drug-like small molecule agents selected from in vitro screening using well-characterized compound libraries (see above) based on parameters such as functional potency, known or potential toxicity liabilities, known pharmacokinetic and absorption-distribution-metabolism-excretion properties, and oral bioavailability;
    • For immunologically targeted interventions, identify, select and prioritize T cell epitopes deemed potentially useful as cancer vaccine antigenic components by using in silico, in vitro, and in vivo immunogenicity testing;
    • For actionable oncotargets that represent previously identified and validated targets as drivers or enhancers of oncogenesis, against which efficacious agents are already available but have not been tested for cancer prevention and interception, evaluate in vivo efficacy of selected agents, utilizing suitable preclinical models known to recapitulate human cancer development for specified target higher-risk cohorts, including the transition from precancer to cancer;
    • Evaluate in vivo efficacy of drugs/drug-like compounds and immunological interventions (e.g., cancer vaccines) selected from in silico and/or in vitro discovery studies, utilizing suitable preclinical models known to recapitulate human cancer development for specified target higher-risk cohorts, including the transition from precancer to cancer.

    (B) Center Organizational Structure. Each U54 CAP-IT Center must be organized as follows:

    1. CAP-IT Center Subunits. Each U54 CAP-IT Center will have interconnected and cooperating subunits with collective scientific expertise and technical capabilities in the areas of "target validation", "screening and identification of active agents or antigenic epitopes", and "in vivo efficacy evaluation". In addition, each CAP-IT Center is expected to have an Informatics group, which can be established within one of the CAP-IT Center subunits or established as a separate Shared Resource Core (see below). CAP-IT Center subunits may be assembled by multiple laboratories and offices from the same institution and/or through multi-institutional arrangements. Each Center can choose how to assemble and organize these Center subunits. When expertise and capabilities of Center subunits are combined, each CAP-IT Center will have all necessary expertise, technical capabilities/skills, and infrastructure to carry out the expected scope of the Center project activities (Also see Section IV Application and Submission Information).

    The Informatics group, regardless of whether established within one of the CAP-IT Center subunits or as a separate Shared Resource Core (see below), is expected to support informatic analyses (bio-, chem- and/or immuno-informatics as needed) and database management activities for the CAP-IT Center. Informatics activities may include but are not limited to bioinformatic analyses of functionally validated precancer and genetic susceptibility oncotargets, molecular and immune oncotarget actionability, druggability, drug-target interactions, feasibility of immune-targetability, epitope prediction, TCR affinity and avidity prediction, and MHC class-I and MHC class-II binding predictions. Project specific databases will be established for data archiving and sharing among the CAP-IT Center project teams. The Informatics group will leverage, where feasible, technology from related NCI-sponsored informatics initiatives, for example, the NCI Informatics Technology for Cancer Research (ITCR) program, which supports the development of algorithms, tools, and resources across the continuum of cancer research. In addition, the informatics group will closely work with the U24 CAP-IT DRCC (RFA-CA-21-039) to establish a centralized CAP-IT database for in-network data archiving and sharing.

    2. Research Projects. Each proposed U54 CAP-IT Center is expected to carry out 3 to 4 Research Projects over the 5-year period. These Research Projects may begin at any point in the agent discovery phase (e.g., target validation, screening and identification of active agents or antigenic epitopes, or in vivo efficacy testing). However, each Research Project's ultimate aim should be to discover molecularly or immunologically targeted agents for cancer prevention and interception for a specified higher-risk cohort regardless of the discovery stage where the Project is originally started.

    Initially, two (2) Research Projects must be proposed in the application. CAP-IT Center applicants are encouraged to propose Research Projects, which are to begin in different phases of agent discovery research (e.g., target validation, screening and identification of active agents or antigenic epitopes, or in vivo efficacy testing). Regardless of the discovery phases of the proposed Research Projects, the number of prevention-interception oncotargets for validation and/or active agents for further testing are expected to be narrowed down as the project progresses from early to late discovery stages, based on the project team’s prioritization criteria and pre-established project workflow.

    During the post-award period, each Center is expected to develop 1 to 2 additional new Research Projects. The Center PD(s)/PI(s) and other designated project team leadership will establish each project-specific research framework, including research objectives and strategies for a well-defined higher-risk cohort (such as a well-characterized HCS cohort), selection criteria for specific organ-sites for a given cohort, oncotarget prioritization criteria, plans for screening and identification of active agents or antigenic epitopes, in vivo preclinical testing strategies, and/or prioritization and selection criteria for discovered interventions for further preclinical development (such as through PREVENT or through partnerships with the private sector) along with the envisioned overall project workflow. The new Research Projects can be based on newly emerging or updated data in the NCI and other program databases (e.g. PCA, CPTAC, CTD2, and EDRN), reported results in the literature, and/or data from the CAP-IT Center investigators' ongoing studies, and will be proposed on a regular basis (quarterly or biannually). All newly proposed Research Projects during the post-award period will be subjected to approval by NCI in accordance with the Cooperative Agreement Terms and Conditions of Awards (Also see Section IV Application and Submission Information).

    3. Core(s). Administrative Core will manage, coordinate, and/or assist all intra-Center research activities and meetings and serve as liaisons between the CAP-IT center subunits, other CAP-IT Centers, and CAP-IT DRCC. In addition, the CAP-IT Center may opt to establish an Informatics Core as a Shared Resource rather than establishing it within one of the CAP-IT Center subunits. The Informatics Core is expected to support informatic analyses (bio-, chem- and/or immuno-informatics as needed) and database management activities for the entire CAP-IT Center. Informatics activities may include but are not limited to bioinformatic analyses of functionally validated precancer and genetic susceptibility oncotargets, molecular and immune oncotarget actionability, druggability, drug-target interactions, feasibility of immune-targetability, epitope prediction, TCR affinity and avidity prediction, and MHC class-I and MHC class-II binding predictions. Project specific databases will be established for data archiving and sharing among the CAP-IT Center project teams. The Informatics Core will leverage, where feasible, technology from related NCI-sponsored informatics initiatives, for example the NCI Informatics Technology for Cancer Research (ITCR) program, which supports the development of algorithms, tools, and resources across the continuum of cancer research. In addition, the Informatics Core will closely work with the U24 CAP-IT DRCC (RFA-CA-21-039) to establish a centralized CAP-IT database for in-network data archiving and sharing.

    (C) Research Team. Each CAP-IT Project will be led by CAP-IT Project team lead investigators, representing each of partnering CAP-IT Center subunits as applicable with assistance from an NCI Program staff member(s) (Project Scientist(s)). Project team leadership will be responsible for establishing a project-specific research framework, including but not limited to specific research aims with a vision for a well-defined higher-risk cohort (such as a well-characterized HCS cohort) and step-wise strategies, including selection criteria for specific organ sites for a given project, oncotarget prioritization criteria, methods of screening and identification of active agents or antigenic epitopes, in vivo testing strategies, agent prioritization criteria, project-specific milestones, and overall project workflow. The CAP-IT Project team leadership will also be responsible for coordinating project activities, overseeing project progress, and making Go/No-Go decisions at critical junctures.

    CAP-IT Network, Governance and Trans-Network Activities

    Because of the complexity and highly specialized nature of research activities required to achieve the Program's research objectives, the CAP-IT network will be formed by up to three U54 CAP-IT Centers (this FOA) and one U24 CAP-IT DRCC (the companion FOA, RFA-CA-21-039) . The ultimate goals of the Program are to advance newly discovered efficacious cancer preventive or interceptive agents to the existing NCI, Division of Cancer Prevention preclinical and clinical development pipelines, PREVENT Program for further development towards IND and Cancer Prevention Clinical Trials Network (CP-CTNet) for early phase clinical trials, and thereby to establish a scientific roadmap and a more streamlined foundational infrastructure for fast-tracking agent discovery and development for cancer prevention and interception from bench to bedside.

    Upon the inception of the Program, the CAP-IT Steering Committee (SC) will be formed, consisting of CAP-IT Center PIs, CAP-IT DRCC PI, and NCI staff members. For details on the composition and responsibilities of the CAP-IT SC, see Section VI.2 under Cooperative Agreement Terms and Conditions of the Award.

    Once the network is established, each CAP-IT Center is expected to develop new additional projects under the direction of the CAP-IT Center PDs/PIs and other designated leadership members. All new CAP-IT projects will be subject to NCI approval in accordance with the Cooperative Agreement Terms and Conditions of Awards.

    CAP-IT Trans-Network Activities applicable to the CAP-IT Centers will include but are not limited to:

    • Interacting with the CAP-IT DRCC to establish a centralized CAP-IT database for in-network data archiving and sharing in accordance with the policies established by the CAP-IT SC;
    • In-network sharing of research tools and resources, such as novel assay technologies, protocols, preclinical biospecimens and agents developed through the conduct of CAP-IT research in accordance with the policies established by the CAP-IT SC;
    • Coordinating, facilitating, and participating in network-wide meetings, such as an Annual CAP-IT Investigators’ Meeting, workshops, seminars and CAP-IT SC meetings.

    Non-Responsive Applications

    The following applications would be considered non-responsive to the CAP-IT Center FOA:

    • Applications that do not include prevention-interception target validation, agent selection or in vivo efficacy evaluation studies that are relevant to the Program's research objectives;
    • Applications that do not propose two initial Research Projects that directly address the Program's research objectives;
    • Applications that propose research activities outside the scope of the Program's expected activities, such as high-throughput screening of large compound libraries, iterative chemical optimization for lead compound identification, advanced preclinical agent development (e.g. IND-enabling studies), or clinical trials.

    It is strongly encouraged that applicants address questions concerning responsiveness to NCI staff contacts listed in Section VII. Agency Contacts, well in advance of the RFA application receipt deadline.

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

    Section II. Award Information

    Funding Instrument

    Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

    Application Types Allowed
    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials.

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIH intends to fund up to three (3) U54 awards, corresponding to a total of $3.6M (in total costs) for fiscal year 2022. It is expected that $3.6M (total costs) per year will be available in subsequent years, but future year amounts will depend on annual appropriations.

    Award Budget

    Application budgets must reflect the actual needs of the proposed center but must not exceed $720,000 per year in direct costs.

    Award Project Period

    5 years.

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

    Section III. Eligibility Information

    1. Eligible Applicants

    Eligible Organizations

    Higher Education Institutions

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

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

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

    Nonprofits Other Than Institutions of Higher Education

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

    For-Profit Organizations

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

    Local Governments

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

    Federal Governments

    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession
    Foreign Institutions

    Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

    Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

    Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

    Required Registrations

    Applicant organizations

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

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
    • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

    Eligible Individuals (Program Director/Principal Investigator)

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

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

    2. Cost Sharing

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

    3. Additional Information on Eligibility

    Number of Applications

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

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

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

    Section IV. Application and Submission Information

    1. Requesting an Application Package

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

    2. Content and Form of Application Submission

    It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

    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:

    Shizuko Sei, M.D.

    National Cancer Institute (NCI)

    Telephone: 240-276-5005

    Email: seis@mail.nih.gov

    Page Limitations

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

    Component Component Type for Submission Page Limit Required/Optional Minimum Maximum
    Overall Overall 12 Required 1 1
    Admin Core Admin Core 6 Required 1 1
    Informatics Core Core 6 Optional 0 1
    Project Project 12 Required 2 2
    Instructions for the Submission of Multi-Component Applications

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

    Overall Component

    When preparing your application, use Component Type ‘Overall’.

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

    SF424(R&R) Cover (Overall)

    Complete entire form.

    PHS 398 Cover Page Supplement (Overall)

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

    Research & Related Other Project Information (Overall)

    Follow standard instructions.

    Project Summary/Abstract: Provide overall goals/abstract/summary for the entire CAP-IT Center application.

    Project Narrative: In the "Project Narrative", it is encouraged that the relevance of the CAP-IT Center research to public health should be stated in lay language, which has been vetted by a cancer research advocate(s) working with the PD/PI team.

    Facilities and Other Resources: In addition to standard items, describe existing facilities and/or other resources (such as existing institutional shared resource facilities) available to the proposed CAP-IT Center. As applicable and pertinent to the proposed research, describe partnerships (e.g., with industrial entities) that will provide relevant capabilities (technology development, fabrication, probes, reagents, cancer biology models, computational expertise, etc.).

    Project/Performance Site Locations (Overall)

    Enter primary site only.

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

    Research and Related Senior/Key Person Profile (Overall) 

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

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

    Budget (Overall)

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

    Travel: Appropriate travel funds must be included in the proposed budget to support travel for at least one CAP-IT PD/PI to participate in an Annual CAP-IT Investigators’ Meeting and/or a SC Meeting, at the NCI’s facilities in Rockville, MD.

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

    PHS 398 Research Plan (Overall)

    Specific Aims: Outline the specific aims for the entire CAP-IT Center, addressing approaches to the discovery of new and innovative targeted agents for cancer prevention-interception. The Specific Aims in this section of the Research Plan should be overarching, high-level, and distinct from the aims of the individual research projects.

    Research Strategy: The Research Strategy must consist of the subsections A-E defined below:

    • Subsection A. Center Overview: Present a concise overall vision and plan for the proposed CAP-IT Center. Focus on the plans for the funding period of the Center and briefly highlight how the Center will lay the groundwork for the eventual discovery of molecularly or immunologically targeted agents that can prevent or intercept oncogenesis in selected higher-risk populations. Without repeating information in individual bio-sketches, describe the applicant’s proposed comprehensive, multi-disciplinary approach and explain how the collective expertise and experience of the investigators will support the team science environment needed to complete the proposed multidisciplinary work. Applications should demonstrate that a Center mechanism is essential to accomplishing the proposed studies.
    • Subsection B. Center Organization and Integration: Include a concise description of the structure of the Center including the organizing framework. Explain how the components of the Center, including key personnel, will interact to form a multidisciplinary team, why each component is essential for addressing the organizing framework of the Center, and how the organization of the components into a Center will create an entity that is greater than the sum of its parts in terms of achieving the Program’s research objectives defined in Section I. Applicants should demonstrate that use of the research Center mechanism is essential to accomplishing studies that would not occur without the climate, facilities, and research resources that a research Center can uniquely provide.
    • Subsection C. Research Projects: Briefly describe each project, including its scientific integration with the proposed organizing framework and a rationale for how each project will help, within the funded period, to generate sufficient results to drive the development of new knowledge on cancer preventive or interceptive oncotargets in higher-risk populations and the discovery of novel targeted interventional strategies based on the proposed organizing framework.
    • Subsection D. Project Development: Briefly describe the process by which the CAP-IT Center will develop new project proposals within the CAP-IT Center in the post-award period (e.g., under the direction of the CAP-IT Center leadership team in coordination with CAP-IT Center subunit investigators and NCI program staff members).

    Subsection E. Shared Resource Cores: Briefly describe any Shared Resource Cores, including the projects supported by the Core(s).

    Letters of Support: Include a letter of support from an institutional official endorsing the proposed CAP-IT Center and describing available institutional resources to support the research. Also include letters from investigators who will serve as consultants or collaborators on the project but with no measurable efforts. Do not include letters from investigators who will have committed efforts in the application.

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

    The following modifications also apply:

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • The Data Sharing Plan should be provided only in the Overall section and encompasses all the activities of the Center;
    • The Data Sharing Plan should briefly describe the types of data and computational resources that are expected to be generated and shared, consistent with achieving the goals of the CAP-IT Center. Data Sharing Plans are expected to describe plans for anonymization, annotation, multimodal data integration; harmonization; transfer learning; and development of robust statistical-, Artificial Intelligence-, and/or Machine Learning-ready datasets to facilitate formats that are accessible to increase the value of these data for sharing with the scientific community.
    • Note that NCI Program staff may negotiate modifications to these plans prior to funding. Specifically, applicants will be expected to abide by the policies and procedures for data, software, and computational model sharing within the context of the NCI Cancer Data Ecosystem including infrastructure and resources for access of multi-modal data, elastic computation, and analysis through the Cancer Research Data Commons developed upon availability (see Section VI: Terms and Conditions of Cooperative Agreement).

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

    PHS Human Subjects and Clinical Trials Information (Overall)

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

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

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Delayed Onset Study

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

    PHS Assignment Request Form (Overall)

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

    Administrative Core

    When preparing your application, use Component Type ‘Admin Core.’

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

    SF424 (R&R) Cover (Administrative Core)

    Complete only the following fields:

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

     

    PHS 398 Cover Page Supplement (Administrative Core)

    Enter Human Embryonic Stem Cells in each relevant component.

     

    Research & Related Other Project Information (Administrative Core)

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

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

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

    Project /Performance Site Location(s) (Administrative Core)

    List all performance sites that apply to the specific component.

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

    List all performance sites that apply to the Administrative Core component. It is anticipated that a CAP-IT Center will centralize the Administrative Core within the applicant institution.

    Research & Related Senior/Key Person Profile (Administrative Core)

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Administrative Core Leader’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
    • An Administrative Core leader may also serve as the CAP-IT contact PD/PI.

     

    Budget (Administrative Core)

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

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

    PHS 398 Research Plan (Administrative Core)

    Specific Aims: Succinctly describe the strategies and goals for managing the CAP-IT Center and connecting the Center to the CAP-IT network.

    Research Strategy: The Administrative Core is expected to have appropriate and effective administrative and organizational capabilities to support the multidisciplinary research teams, foster synergy and integration of the CAP-IT Center, and support planning and evaluation activities. The Administrative Core will support and coordinate project administration within the Center and coordinate participation in the CAP-IT SC:

    Under Approach, describe the administrative structure to support the proposed CAP-IT Center, including but not limited to:

    • Management and Communication Plan: Describe the plans for management and integration of Center activities and communication and evaluation of progress across the Center. Describe the leadership and communication strategies to manage and track progress of the multiple projects and sites that make up the Center. Include a description of the Center leadership structure and concisely describe oversight mechanisms that will be used by the CAP-IT Center PD/PI(s). Describe any provisions for the mentoring and development of new investigators. ;
    • Annual Meeting and Other Network Activities: Provide a brief description of strategies for connecting and integrating the Center with the CAP-IT network. Funded Centers are expected to participate in an Annual Investigators’ meetings to present results and to communicate with other CAP-IT investigators. The Center PD(s)/PI(s) are expected to attend the Annual Meeting and participating faculty, postdoctoral associates, graduate students, and other Center members are all encouraged to attend. The Center PD/PI (contact PD/PI for applications with multiple PDs/PIs) is expected to participate in CAP-IT's SC. The CAP-IT Centers are also encouraged to organize and participate in other Program meetings and workshops, organize collaborative activities, promote Trans-Network collaborations, and organize and participate in scientific and programmatic working groups;
    • Outreach plan: Provide a plan that describes how outreach will be conducted to promote the Program's research objectives , engage the biomedical community on precision cancer prevention-interception, provide research experiences to students, postdocs and early-stage investigators in precision cancer prevention interception, and disseminate advances and capabilities of the CAP-IT Center to the broader cancer research community. The proposed activities should relate to and integrate with the organizing framework of the Center. Potential activities include, but are not limited to, conferences, workshops, seminar series, skills development , personnel exchanges, and development of a Center website;
    • Center and Program Evaluation: Describe how the Administrative Core will coordinate participation in Center program evaluation activities, including progress reports, site visits, and providing additional communication and materials to the NCI as needed. Describe the milestones and/or metrics for determining success during the CAP-IT award period and how unanticipated obstacles to the plan may be overcome.

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

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • Resource Sharing Plans should only be included in the Overall component

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

    PHS Human Subjects and Clinical Trials Information (Administrative Core)

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

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

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Delayed Onset Study

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

    Research Projects

    When preparing your application, use Component Type ‘Research Project.’

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

    SF424 (R&R) Cover (Research Projects)

    Complete only the following fields:

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

    PHS 398 Cover Page Supplement (Research Projects)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Research Projects)

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

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

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

    Project /Performance Site Location(s) (Research Projects)

    List all performance sites that apply to the specific component.

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

    List all performance sites that apply to the Administrative Core component. It is anticipated that a CAP-IT Center will centralize the Administrative Core within the applicant institution.

    Research & Related Senior/Key Person Profile (Research Projects)

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Administrative Core Leader’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
    • An Administrative Core leader may also serve as the CAP-IT contact PD/PI.

    Budget (Research Projects)

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

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

    PHS 398 Research Plan (Research Projects)

    Each CAP-IT Center is required to have two Research Projects at the time of the Award.

    Specific Aims: Describe the goals of each proposed Research Project and key milestones.

    Research Strategy: Applicants should use the standard structure of the Research Strategy section (i.e., sub-sections Significance, Innovation, and Approach) defined in the SF424 Application Guide with additional guidance as defined below.

    Address the following additional aspects for each individual Research Project:

    • Integration: Provide a rationale for how it fits into the proposed framework of the Center and explain its progression plan(s) through inter-subunit coordination within the CAP-IT Center;
    • Project Timeline: A timeline (Gantt chart) including milestones is required. Milestones are intermediate steps towards the completion of concrete goals, which create go/no-go decision points in the project and must include clear and quantitative criteria for success. Yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Milestones and the timeline must be provided in a separate heading at the end of the Approach section.

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

    ? Resource Sharing Plans should only be provided in the Overall Component of the application.

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

    PHS Human Subjects and Clinical Trials Information (Research Projects)

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

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

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Delayed Onset Study

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

    Shared Resource Core

    When preparing your application, use Component Type ‘Shared Resource Core’

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

    SF424 (R&R) Cover (Shared Resource Core)

    Complete only the following fields:

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

    PHS 398 Cover Page Supplement (Shared Resource Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Shared Resource Core)

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

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

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

    Project /Performance Site Location(s) (Shared Resource Core)

    List all performance sites that apply to the specific component.

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

    List all performance sites that apply to the Administrative Core component. It is anticipated that a CAP-IT Center will centralize the Administrative Core within the applicant institution.

    Research & Related Senior/Key Person Profile (Shared Resource Core)

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Administrative Core Leader’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
    • An Administrative Core leader may also serve as the CAP-IT contact PD/PI.

    Budget (Shared Resource Core)

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

    The Core Lead(s) must each commit and maintain through the life of the award a minimum of 0.6 calendar months per year of effort. If there are multiple co-leads, it is not necessary that each commit equal effort to the project.

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

    PHS 398 Research Plan (Shared Resource Core)

    Specific Aims: Outline the goals of each Shared Resource Core. Indicate which specific Research Projects will be supported by the Core.

    Research Strategy: The optional Shared Resource Cores may be physical or virtual infrastructures providing resources that support the CAP-IT Center components in their activities. Each proposed Shared Resource Core is expected to support two or more Research Projects. At a minimum, address the following aspects:

    • Explain the structure of the optional Shared Resource Core;
    • Justify why the Shared Resource Core is needed and how it will facilitate Research Projects;
    • Define the services and resources that the Core will provide to the CAP-IT Center components and explain the value of the Core services to the Center and Research Projects;
    • Address other relevant issues, such as integration between the Core and Research Projects, quality control, procedures for prioritizing Projects to use the Core and allocating resources, cost effectiveness, and increased efficiency. Training in complex techniques and methods should be described if they are functions of the proposed Core.

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

    ? Resource Sharing Plans should only be provided in the Overall Component of the application.

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

    PHS Human Subjects and Clinical Trials Information (Shared Resource Core)

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

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

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Delayed Onset Study

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

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

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

    4. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

    Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

    Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

    Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

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

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

    7. Other Submission Requirements and Information

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

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

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

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

    Important reminders:

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

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

    See more tips for avoiding common errors.

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

     

    Post Submission Materials

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

    Section V. Application Review Information

    1. Criteria

    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 FOA, note the following:

    Reviewers will provide an overall Impact Score for the entire CAP-IT Center (Overall component) and numerical score for individual components (individual Research Projects, Administrative Core, and if applicable Shared Research Core(s)). Reviewers will be assigned to evaluate the entire application.

    For the evaluation of the CAP-IT Center application, the Research Projects will be assessed as the scientific basis of each Center , with additional components enhancing and integrating the overall research program. The overall Impact Score will reflect the synergy and integration provided by inclusion of each CAP-IT Center component.

    Overall Impact - Overall

    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).

    Scored Review Criteria - Overall

    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?

    Specific to this FOA:

    Given the organizational framework, vision, and scientific focus of the proposed CAP-IT Center, what is the likelihood that the research of the proposed Center will substantially advance the understanding of cancer preventive-interceptive oncotargets in higher-risk populations and the discovery of novel targeted interventional strategies for precision cancer prevention and interception? How well does the Center address a research issue that could not be addressed by a single research project? Are the CAP-IT Center components and the investigator team well integrated to collectively support the overarching goals of the Center ?

    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?

    Specific for this FOA: Are the backgrounds, expertise, and commitments of the PD(s)/PI(s) and other key persons sufficient for the proposed scope of activities Is the proposed research team sufficiently multi-disciplinary to achieve a comprehensive approach that can span from basic biological mechanistic studies of validating oncotargets to innovative small molecule or immunological agent discovery? Does the proposed CAP-IT Center combine/integrate/maximize team science productivity between expert investigators in the necessary disciplines towards a common goal over the funded period?

    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?

    Specific for this FOA: Does the proposed CAP-IT Center explore innovative biological concepts to improve the understanding and knowledge of cancer preventive or interceptive oncogenic targets and to discover novel targeted interventional strategies for precision cancer prevention-interception? How novel are the research methods proposed to validate potential oncotargets and discovering efficacious molecularly or immunologically targeted agents for higher-risk populations?

    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?

    Specific for this FOA: How well does the application justify the structure of the CAP-IT Center to accomplish the proposed goals of the Center How well does the proposed CAP-IT Center take advantage of multidisciplinary approaches for a comprehensive study that encompass biological mechanisms of oncogenesis, target validation, and/or the discovery of novel cancer preventive or interceptive interventions for higher-risk populations? Does each Research Project specify target higher-risk population(s)? Are effective mechanisms in place to foster strong collaborative interactions and promote “cross-fertilization” among investigators and participating laboratories/institutions? Are mechanisms for facilitating sharing of samples and resources well planned or in place as appropriate ?

    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?

    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?

    Specific to this FOA: Will the scientific environment at the participating institutions stimulate trans-disciplinary research collaborations? Do multi-institutional teams take advantage of the distinctive strengths available through multi-institutional collaborations, where appropriate?

    Additional Review Criteria - Overall

    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.

    Scored Review Criteria - Research Project

    Reviewers will consider each of the review criteria below to assess the scientific merit and give a separate score for each Research Project.

    Significance

    • How well does the proposed research project address an important problem related to the mechanisms of oncogenesis, selection of exploitable oncogenic targets and pathways and the discovery of novel cancer preventive or interceptive interventions in higher-risk populations? Is the prior research that serves as the key support for the proposed project rigorous? If the aims and milestones of the project are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods in the field of precision cancer prevention-interception?

    Investigator(s)

    • Are the investigators appropriately trained and well suited to carry out this work? Is the project proposed appropriate to the experience and expertise of the project leader and other researchers and team members?

    Innovation

    • How well does the proposed project employ novel concepts, novel multi-disciplinary approaches, and/or novel methods to solve the problem stated in the study? Are the aims original and innovative? How does the project challenge existing paradigms or develop new methodologies, theories, and/or technologies?

    Approach

    • Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the proposed project specify target higher-risk population(s)? How adequate are the strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? How adequate are the plans the investigators presented to address relevant biological variables, such as sex, for studies in vertebrate animals? As appropriate, how well are the potential problems and alternative approaches considered? To what extent are the project timeline and milestones appropriate and realistic for the proposed research objectives?

    Environment

    • How well does the scientific environment in which the work will be done contribute to the probability of success? How well do the proposed experiments benefit from unique features of the scientific environment or employ useful collaborative arrangements?

    Review Criteria-Administrative Core

    Reviewers will provide only one overall adjectival impact score for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects for the Administrative Core while determining scientific and technical merit of the application:

    • Does the proposed Administrative Core address the needs of the CAP-IT Center that it will coordinate and serve? Is the scope of activities proposed for the Administrative Core appropriate to meet those needs?
    • How well suited are the PD(s)/PI(s) and other personnel to their roles in the Administrative Core? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing research? Do the investigators demonstrate significant experience with coordinating collaborative research in the relevant field? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills? How appropriate are their leadership approach, governance, plans for conflict resolution, and organizational structure for the CAP-IT Center? Does the applicant have experience overseeing selection and management of subawards, if needed?
    • Does the application propose novel organizational concepts or management strategies in coordinating the research program of the CAP-IT Center? Is a refinement, improvement, or new application of organizational concepts or management strategies proposed?
    • How well-reasoned and appropriate are the overall strategy, operational plan, and organizational structure to accomplish the goals of the research program of the CAP-IT Center? To what extent does the proposed approach address the communication and management needs of the CAP-IT Center and provide appropriate plans for participation in the Annual CAP-IT Investigators' meeting and other meetings? How well do the Outreach plans address providing opportunities to students, postdocs and early-stage investigators for skills development and research experiences in precision cancer prevention and interception and communication opportunities for the CAP-IT Center? To what extent does the applicant address Center program evaluation activities? Are potential problems, alternative strategies, and benchmarks for success presented? Does the proposed strategy for the Administrative Core adequately establish feasibility and manage the risks associated with the activities of the Center? Are appropriate plans for workflow and a well-established timeline proposed? How effectively will the Center be able to coordinate the efforts of its participating institutions as well as coordinate its efforts with those of the entire CAP-IT Center?
    • How will the institutional environment in which the Administrative Core will operate contribute to the probability of success in facilitating the research of the CAP-IT Center it serves? How adequate are the institutional support, equipment, and other physical resources available to the investigators adequate for the Administrative Core proposed? How will the Administrative Core benefit from unique features of the institutional environment, infrastructure, and/or personnel? Are resources available within the scientific environment to support electronic information handling?

    Review Criteria-Shared Resource

    Reviewers will provide only one overall adjectival impact score for the Shared Resource Core if proposed (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of the application:

    How well matched is the proposed Shared Resource Core to the needs of the overall CAP-IT Center? Are the services of the Shared Resource Core critical to the goals of more than one Research Project? Are the qualifications, experience, and effort commitment of the Shared Resources Core Director(s) and other key personnel adequate and appropriate for providing the proposed facilities or services? Will the proposed Shared Resource Core provide cost effective services to the CAP-IT Center, prevent duplication, and/or increase efficiency?

    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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    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

    Additional Review Considerations - Overall

    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 following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan.

    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 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 FOA.

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

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

    3. Anticipated Announcement and Award Dates

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

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

    Section VI. Award Administration Information

    1. Award Notices

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

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

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

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

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

    Prior Approval of Pilot Projects

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

    2. Administrative and National Policy Requirements

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

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

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

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

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

    Cooperative Agreement Terms and Conditions of Award

    The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and 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 awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

    The PD(s)/PI(s) will have the following primary responsibilities:

    • Planning and conducting the operations defined by the terms and conditions of the cooperative agreement award. This includes determining research approaches, designing protocols, setting project milestones in consultation with NCI staff, and ensuring scientific rigor.
    • Conducting the scientific research in the project, reporting progress on milestones or objectives to NCI staff, and reporting results to the scientific community.
    • Assuming responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research and administrative functions supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies.
    • Participating in a cooperative, interactive, and collaborative manner with NCI staff, other CAP-IT network investigators, and one another to maximize impact of the CAP-IT network and meet Program goals and objectives.
    • Serving as voting members of the CAP-IT SC that is responsible for the governance of CAP-IT activities (as described below).
    • Accepting and implementing the goals, priorities, procedures, protocols, and policies agreed upon by the CAP-IT SC.
    • Maintaining the confidentiality of the information developed or handled by the CAP-IT, including, without limitation, unpublished data, protocols, data analysis, confidential exchanges between members of the CAP-IT, as well as any confidential information received by third party collaborators.
    • Facilitating the public release and dissemination of results, data, reagents, models, technologies and other products generated through this award in a timely manner. The PD/PI is expected to share data and resources generated through this award in accordance with the approved plan for making quality-assured data and materials available to the scientific community and the NIH as written in the final version of the grant application, and consistent with sharing policies and recommendations developed and approved by the CAP-IT SC, NIH sharing policies, and the goals of the FOA.
    • Ensuring that any industry collaborations should be governed by a research collaboration agreement with terms that ensure the collaboration is conducted in accordance with the applicable NIH policies and procedures and any policies and procedures developed by the SC.
    • Operating in accordance with processes and goals as delineated in the FOA, and in accordance with processes, goals, and procedures established by the SC to the extent of applicable grant regulations.
    • Awardees will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and network policies agreed upon by the CAP-IT SC, to the extent consistent with grants regulations. This includes compliance with program policies and procedures including, as applicable, the use of common protocols, publication of study results, collaborative procedures, confidentiality, and sharing plans to be developed by the SC in collaboration with NCI.
    • Attending an Annual Investigators' Meeting of the CAP-IT PDs/PIs.
    • Adhering to a Network Communication Plan: A consensus Communication Plan will be drafted by the CAP-IT SC during the kickoff meeting of the CAP-IT. This plan will clearly spell out interactive requirements that all CAP-IT investigators are expected to follow, including:
      • Participation in regular conference calls with fellow CAP-IT colleagues through contribution to various sub-committees and working groups;
      • Participation and presentation of findings at the CAP-IT Annual Investigators' Meeting;
      • Coordination of efforts with other members of the CAP-IT;
      • Jointly publishing on CAP-IT collaborations in a timely manner
    • Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

    An NCI Program Director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Additionally, an NCI Program staff member(s) will act as a Project Lead Scientist(s) to assist the project team leadership and will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may be designated to have substantial involvement (as Project Scientists). The specific functions of the substantially involved NCI staff include, but not limited to the following activities:

    • Advising the awardees on specific scientific issues as well as programmatic priorities.
    • Serving as NCI lead Project Scientists and a voting member of the CAP-IT SC.
    • Co-organizing and participating in CAP-IT SC meetings, CAP-IT Annual Investigators' meetings, specialized workshops, seminars, and webinars.
    • Assisting in the management of the CAP-IT SC including the development of draft sharing and operating policies that are in accordance with NIH guidelines.
    • Serving as a resource for the CAP-IT Centers and the network as a whole in promoting interactions with other ongoing NCI activities that may be relevant to the goals of the CAP-IT and facilitating access to databases, technical capabilities, and other resources available through NCI to which the teams may have access.
    • Facilitating collaborative research efforts that involve multiple CAP-IT Research Centers.
    • Monitoring the performance of the Program, making recommendations on overall directions and efficient utilization of resources, and minimizing unwarranted duplication of effort across the Program.
    • Reviewing the progress of individual research projects and collaborative activities between the program participants and making recommendations on overall project directions.
    • Reviewing the compliance of CAP-IT awardees with the recommendations developed by the Steering Committee and coordinating external evaluation of CAP-IT
    • Recommending topics and initiatives for the use of CAP-IT supplemental funds that may be available for CAP-IT members to collaborate with researchers external to the Program.
    • The NCI reserves the right to adjust funding or withhold future support on any CAP-IT award in the event of: (1) a substantial shortfall in accomplishing the CAP-IT Center management goals and responsibilities as stated in the reviewed application; (2) a failure to meet CAP-IT policies and procedures; (3) substantive changes in the management structures of the CAP-IT Center that are not in keeping with the objectives of the FOA; and/or (4) failure to make substantial progress towards milestones with the go/no-go decision points as established by the CAP-IT project leadership.
    • The NCI will have pre-publication access to the data generated and will periodically review the data, with the intent of facilitating optimal integration and dissemination of the results. Awardees will engage in data sharing in accordance with the CAP-IT network policies as established by the SC and within NIH guidelines. However, the awardees will retain custody and primary rights to their data developed under these awards. NIH and NCI will encourage timely publication of findings and public access to publications.

    Areas of Joint Responsibility include:

    CAP-IT will have a Steering Committee as the main governing body. The CAP-IT SC will consist of the following voting members:

    • The PDs/PI(s) of each awarded CAP-IT Center (or senior investigator as proxy when applicable) will collectively have one vote;
    • The PDs/PI(s) of an awarded CAP-IT DRCC Center (or senior investigator as proxy when applicable) will collectively have one vote; and
    • The NCI Project Scientists collectively have one vote for the NCI.

    Additional NIH/NCI program staff and other government staff may participate in CAP-IT Steering Committee meetings as non-voting members. The structure is designed to allow awarded investigators and NCI staff to work together to facilitate trans-CAP-IT activities based on synergistic expertise and projects.

    Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members.

    The SC may decide to establish subcommittees for specific purposes. The NCI Project Scientists and Program Officers will serve on such sub-committees, as they deem appropriate.

    PD/PI representing one of the CAP-IT Centers or the CAP-IT DRCC will be selected to serve as a chairperson of the SC on a rotating basis following award issuance. All CAP-IT SC decisions and recommendations that require voting will be based on a majority vote.

    The CAP-IT Steering Committee will meet virtually quarterly (and on an ad hoc basis as needed) and in-person once a year at the CAP-IT Annual Investigators' Meeting. TheCAP-IT SC responsibilities include:

    • Developing collaborative protocols and CAP-IT network policies, including but not limited to centralized data management and in-network data and resource sharing policies;
    • Identifying scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and developing recommendations to NIH/NCI Program Officials as appropriate;
    • Reviewing the potential of shared support infrastructure(s) at individual CAP-IT Centers and the CAP-IT DRCC to serve the needs of the entire CAP-IT program;
    • Facilitating communication and fostering collaborations across CAP-IT;
    • Identifying opportunities for sharing techniques, materials, information and tools developed within each individual CAP-IT member center;
    • Evaluating collaborative activities, and providing feedback to the NCI Program Staff;
    • Ensuring that CAP-IT Centers and CAP-IT DRCC leverage, where feasible, resources and technology from NIH and NCI-sponsored initiatives and tools, for example the NCI Informatics Technology for Cancer Research (ITCR) program, which supports the development of algorithms, tools, and resources across the continuum of cancer research;
    • Co-leading the planning of major events such as the CAP-IT Annual Investigators’ Meeting
    • Discussing important issues relevant to targeted agent discovery for precision cancer prevention-interception;
    • Reviewing progress of CAP-IT research towards meeting the overall Program goals and determining future directions for the network;
    • Developing publication policies to facilitate collaborations and co-publications by CAP-IT members;
    • Making recommendations on the possible use of any supplemental funds that may be available for collaborations with members of the scientific community external to CAP-IT;
    • Discussing implementation of recommendations or suggestions from the NCI and any external consultants and plan a timely implementation strategy; and
    • Coordinating dissemination of Network output to the broader cancer research community.

    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 CAP-IT SC 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 awardee. This special dispute resolution procedure does not alter the awardee'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. Reporting

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

    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.

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

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

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

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

    General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Shizuko Sei, M.D.

    National Cancer Institute (NCI)

    Telephone: 240-276-5005

    Email: seis@mail.nih.gov

    Peer Review Contact(s)

    Referral Officer
    National Cancer Institute (NCI)
    Telephone: 240-276-6390
    Email: ncirefof@dea.nci.nih.gov

    Financial/Grants Management Contact(s)

    Amy Bartosch
    National Cancer Institute (NCI)
    Telephone: 240-276-6885
    Email: amy.bartosch@nih.gov

    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.

    Authority and Regulations

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


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