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

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) intends to support a consortium of Cellular Cancer Biology Imaging Research (CCBIR) Centers. The overall purpose of the CCBIR initiative is to facilitate innovation in advanced imaging technologies that could be applied to fundamental basic and pre-clinical research problems in cancer biology. The CCBIR Centers are expected to develop and test imaging technologies that are suitable for extracellular to cellular and subcellular resolution and applicable to specific areas/problems of basic and/or pre-clinical cancer research.

The long-term goal of the CCBIR Program is to foster a sustainable collaborative community that promotes synergies between imaging technology developers and cancer biology researchers.

Each proposed CCBIR Center should be uniquely positioned to address cancer research problems that:

• Are solvable by the development of innovative advanced cellular imaging approaches; and
• Have potential for transformative impact on cancer biology research by either expanding current concepts or creating new fundamental lines of basic and/or pre-clinical cancer research leveraging the imaging toolkit(s) created over the award period.

Each proposed CCBIR Center should be designed as a research resource environment focused on a specific cancer biology problem (a Center's "Theme") that will drive and guide innovation in cellular imaging technologies to be developed. Accordingly, the workflow design of proposed CCBIR Centers must be based on iterative cycles of imaging technology development that flow into a cancer biology research test-bed for newly developed technology validation, which in turn motivates the next cycle of technical refinement, experimental optimization, and innovation.

Key Terms for This FOA

CCBIR Center Theme: A specific cancer biology research area or problem that defines the scientific focus of a given CCBIR Center. All the Center's imaging technology development efforts must be driven by and directly relevant to this Theme.

CCBIR Technology Development Unit (TECH): The imaging technology functional Unit of the CCBIR Center is responsible for driving the design, fabrication, and development of new technologies. The TECH Unit should ensure integration and interoperability of technologies that will ultimately comprise an integrated imaging toolkit for cancer biology end-users focused on the Center Theme.

CCBIR Research Test-Bed Unit (RTB): The cancer biology functional Unit of the CCBIR Center is responsible for conducting cancer biology experiments that demonstrate the capabilities and identify limitations of technologies developed by the TECH Unit, thereby, facilitating the next cycle of refinement and optimization.

Integrated Imaging Toolkit: A functionally cohesive suite of imaging technologies that end-users would utilize to conduct imaging experiments relevant to the CCBIR Center Theme. Toolkits may be comprised of instrumentation, associated specialized devices, reagents, probes, and operating and data handling software.

Advances in imaging from the extracellular to cellular and subcellular scales have revealed structures and processes that were heretofore unknown. These innovative technologies provide mechanistic insights into cellular organization and dynamics in both time and space and have significantly accelerated new understanding in the biological sciences. Imaging technologies, such as super-resolution microscopy, adaptive optics, mass-spectrometry-based imaging, and optogenetic probes, offer transformative potential for new understanding in basic and pre-clinical cancer biology research. Cancer research could benefit from the implementation of advanced cellular imaging modalities that enable exploration of the states and dynamic processes across diverse types of cancer at the extracellular to cellular and subcellular length scales. Imaging cancer at these scales entails challenges inherent to cancer biology that are less common when imaging normal cell physiology. The phenotypic diversity in the myriad of cancer cell types, dynamic-longitudinal changes, and different site-specific contextual microenvironments often necessitate modifications and optimization in approaches, methods, and instrumentation. Additional barriers often exist in both cost and access to infrastructure requisite for high-end imaging. The NCI is launching the CCBIR Program to support the combination of technology development with discovery science and foster the implementation and wider dissemination of advanced instrumentation, allied devices, and probes designed specifically to enable mechanistic hypothesis testing in the cancer research community, notably in the emerging areas of imaging live cell dynamics and fundamental cancer biology processes. The cadre of CCBIR Centers will be comprised of multidisciplinary teams of imaging technology innovators and cancer cell biologists who will work together to address fundamental challenges in cancer research.

Scientific Focus--Center Theme

To be responsive to this FOA, each CCBIR Center proposed must explicitly address a fundamental challenge(s) in basic cancer biology and/or pre-clinical cancer research specific to a thematic subject area that defines the Center.

Examples of CCBIR Center Themes include, but are not limited to, the following:

• Cancer health disparities;
• Tumor microenvironment;
• Invasion and metastasis;
• Immuno-oncology;
• Therapy resistance;
• Cell plasticity;
• Cancer stem cells;
• Metabolic reprogramming;
• Oncogenic signaling;
• Redox biology.

A CCBIR Center application may propose to either specialize expertise in a specific type of cancer, or multiple cancer types as appropriate to examine the cancer biology process(es) that defines the central Center Theme.

Examples of cancer biology questions include, but are not limited to, the following:

• Can quantification of cellular to subcellular morphometric dynamics and biophysical-state changes point to mechanisms of action for cancer therapies, predict resistance/sensitivity, and resolve off- target effects?
• What are the spatiotemporal complexities and hierarchies of oncogenic signaling at subcellular scales, and do they predict oncogenic behaviors, or reveal potential targets for therapy?
• How do details in spatial and temporal patterns at the subcellular scale relate to higher dimensions of single cell behaviors and/or inform on population dynamics in the tumor microenvironment and evolution of resistance to therapies?
• How are dynamic gradients in cellular effectors (e.g., cytokines, metabolites, redox species) functionally connected in time and space to specific cancer cell phenotypic behaviors?

Imaging Technologies and Approaches

It is expected that addressing the research needs associated with the Center's Theme will require multiple, complementary cellular imaging-based technologies and approaches. Accordingly, the proposed CCBIR Centers must be able to develop appropriate integrated imaging "toolkits" during the award period. Each toolkit must have all of the following characteristics:

• The tools must be developed in close collaboration with their ultimate user, i.e., basic or pre-clinical cancer biology researchers;
• The toolkit must be designed as an interoperable system (a suite of complementary imaging tools);
• Orthogonal toolkits suitable for distinct context of use (e.g., live versus fixed cells/tissue) may be developed in parallel or tandem as appropriate for the Center's Theme;
• As appropriate for the Center's Theme, the tools can include a combination of new technologies and methods as well as the adaptation or improvement of existing technologies;
• Whereas not all the tools need to be newly developed or innovative, collectively as an integrated toolkit, they should offer a unique, potentially transformative potential to open new directions in research on the fundamental problem(s) underlying the Center's Theme;
• Toolkits with potential to integrate high-risk lines of investigation may be justified. It is expected that some levels of risk at earlier stages of development will be proportionally mitigated as tools undergo the required iterations between the Technology Development (TECH) and Research Test Bed (RTB) units.

Categories of Imaging Approaches and Techniques

Imaging approaches chosen may include a range of technologies/platforms. Examples include, but are not limited to the following:

• Force microscopy (e.g., atomic force microscopy, traction force microscopy);
• Visible light-band optical microscopy (e.g., intravital microscopy, expansion microscopy, lattice light sheet microscopy, optical coherence tomography, structured illumination microscopy, super-resolution microscopy, fluorescence lifetime imaging, fluorescence-resonance energy transfer imaging, adaptive optics, photoacoustic microscopy, pump-probe spectroscopy);
• Mass-spectrometry-based imaging (e.g., accelerator mass spectrometry, laser ablation-inductively coupled plasma-mass spectrometry, nano-secondary ion mass spectrometry); and/or
• Electromagnetic radiation-based microscopy (other than light-band; e.g., coherent anti-Stokes Raman scattering, Fourier transform infrared micro-spectroscopy, high resolution magnetic resonance microscopy, infrared synchrotron beam spectrometry, Raman spectroscopy, synchrotron-based X-ray fluorescence microscopy);
• Hyperspectral imaging.

Types of Research Tools and System Workflows to Develop

It is expected that the cellular imaging research toolkits to be developed by a CCBIR Center will include a distinctive and integrated combination of various types of tools as appropriate. These tools may range from new instrumentation, novel methods using existing instrumentation, and various associated specialized devices, reagents, probes, software, data handling methods, etc. System workflows may be devised to combine imaging with allied complementary approaches that enable co-registration across multiple length scales (e.g., correlative light and electron microscopy), a combination of orthogonal modalities, or an integration between live cell imaging and various -omics methods. Chemical, molecular, genetically-encoded, optogenetic or otherwise functionalized probes relevant and enabling for both the CCBIR Center's imaging technologies and cancer biology Theme are anticipated.

Team Expertise

To address the goals of this FOA, the team of the proposed CCBIR Center must include, at a minimum, the following types of experts:

• Cancer biologists actively pursuing the areas of cancer research that form the Center's Theme;
• Imaging researchers, technologists, imaging tool developers, probe developers, etc., as needed for the creation and integration of an imaging toolkit(s) for the Center's Theme; and
• Experts in advanced computational and image analysis approaches necessary to support data efforts (e.g., acquisition, processing, harmonization).

CCBIR Center Structure

Each CCBIR Center is required to contain three essential and interconnected structural/functional units:

• Administration and Coordination Core (ACC);
• Imaging Technology Development Unit (TECH); and
• Cancer Biology Research Test-Bed Unit (RTB).

The expected responsibilities of these units are as follows:

Administration and Coordination Core (ACC). The ACC will be responsible for:

• Overarching leadership, coordination, and direction to the TECH and RTB units of the Center (including overseeing the iterative cycles of projects between TECH and RTB Units);
• Effort coordination across the participating institutions, including, if applicable and appropriate, any commercial or foundation entities;
• Implementing strategies to increase representation and training of underrepresented minorities in the biomedical research workforce who will participate in the Center’s research program;
• Partnering with a cancer research advocate (or patient advocate) to engage and participate in Center activities, including but not limited to the steering committee and annual meetings and scientific outreach.

Imaging Technology Development Unit (TECH) and Research Test-Bed Unit (RTB). The required interconnected relationship between the TECH and RTB units facilitates a flow between design, development, and application activities driven by the CCBIR Center's Theme. The TECH Unit must be capable of supporting the full spectrum of technology development, including early stage high-risk lines of investigation, and improvements to evolving toolkit technologies within the context of iterative engagement with the RTB Unit. Results from demonstration activities in the RTB Unit in initial stages of the award period will inform feasibility, with later cycles incorporating issues related to interoperability, and ultimately optimization of imaging toolkits. TECH lines of investigation that encompass a range of research and development on instruments and other specialized devices, reagents, probes, software, and data handling methods may begin as parallel tracks that merge as an integrated toolkit after refinement through iterative cycles with the RTB Unit. As appropriate for context of use, orthogonal imaging toolkits may be produced (e.g., toolkits for imaging live cells versus specimens).

It is anticipated that an iterative cycle of both technological and intellectual development flowing between TECH and RTB units will be coordinated by the Administration and Coordination Core to ensure a continued engagement by all parties that escalates in sophistication over the project period. Ideally, the interconnected structure of the CCBIR Center must lead to integrated imaging toolkit(s) that as a whole are novel and aptly address the significant challenge(s) in cancer biology research defined by the CCBIR Center Theme.

External Advisory Panel (EAP): Each awarded CCBIR Center must recruit external experts (from outside the Center) who will serve as scientific advisors to the CCBIR Center leadership. This EAP will be advising the Center on prioritization and timing of TECH-RTB iteration cycles and strategic planning for future research directions. The EAP is expected to have experts from the fields of imaging technology and cancer biology.

CCBIR Steering Committee: The consortium of CCBIR Centers will be governed by the CCBIR Steering Committee. Details on the composition and responsibilities of the Steering Committee are provided in Section VI.2 under Cooperative Agreement Terms and Conditions of the Award.

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

• Applications that do not use the required CCBIR Center structure (ACC, TECH Unit, and RTB Unit);
• Applications seeking to advance a single technology or technologies that are not related to imaging at the subcellular to extracellular length scales or the Center Theme;
• Technology development applicable for medical imaging modalities that are not integrated with imaging with resolution at the subcellular and/or extracellular length scales;
• Applications focused only on whole body imaging approaches;
• Applications focused only on biophysical approaches;
• Applications focused heavily on computational approaches for imaging or informatics manipulations and analyses.

IMPORTANT NOTE:

Researchers uncertain as to whether their intended framework for a CCBIR Center meets the requirements of this FOA are encouraged to contact NCI scientific staff listed in Section VII. Agency Contacts.

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

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

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

Applicant Organizations

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

• 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.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• 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.

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.

Applicants proposing multiple PDs/PIs are encouraged to consider a team of at least one PD/PI with primary expertise in cancer biology research and at least one PD/PI with primary expertise in cellular imaging technology.

Any individual designated as a PD/PI must not be designated as a PD/PI on another CCBIR Center application.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. 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).

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

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

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

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

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

The letter of intent should be sent to:

Nastaran Zahir, Ph.D.

Division of Cancer Biology
National Cancer Institute (NCI)
Telephone: 240-276-6333
Email: nas.zahir@nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall (use for "Center Overview")	6
Admin Core (use for "Administration and Coordination Core)	6
TECH (use for Technology Development Unit)	12
RTB (use for Research Test-Bed Unit)	12

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

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

The application should consist of the following components:

• Overall: required, maximum of 1
• Admin Core: required, maximum of 1
• Technology Development (TECH) Unit: required, maximum of 2
• Research and Test-Bed (RTB) Unit: required, maximum of 2

When preparing your application, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions.

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

Project Narrative: In the "Project Narrative", the relevance of the CCBIR Center research to public health should be stated in lay language that is vetted by the cancer research advocate 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 cores) available to the proposed CCBIR 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.).

Enter primary site only.

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

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

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

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

• Personnel Costs: Senior/Key Personnel and Other Personnel. The request under this category may include estimated costs of salary support (based on level-of-effort) for the PD(s)/PI(s) and other personnel responsible for the various aspects of operation within the functional components of the CCBIR Center that must be commensurate with the efforts needed for their expected involvement.
• A minimal effort level of 0.96 person-months is required for the contact PDs/PIs for multi-PI applications and 1.2 person-months for single PI applications as described for multi-component applications in the NCI policy NOT-CA-20-047; the level of effort cannot be reduced below that level during the entire project period.
• Travel: Appropriate travel funds must be included in the proposed budget to support travel for at least one CCBIR PD/PI to participate in an Annual CCBIR Program Investigators Meeting and/or a Steering Committee Meeting.

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

Specific Aims: Outline specific aims for the entire CCBIR Center. Address, as appropriate, goals for the TECH and RTB Units.

Research Strategy: Provide an overview of the proposed CCBIR Center, addressing all the aspects identified below for the TECH and RTB Units.

• The scientific focus in basic cancer biology research that defines the Center's Theme;
• The significance of the proposed research in terms of timeliness and potentially transformative outcomes in the context of currently available cellular imaging technologies as well as other ongoing technology development efforts;
• The rationale for the overall proposed technical approach(es) intended to address the specific research challenges that define the Center;
• The overall philosophy and workflow that will be used to guide the iterative relationship between the TECH and RTB units to make an impact on the basic cancer biology research challenge(s) that defines the CCBIR Center's Theme;
• A timeline that illustrates the CCBIR Center's vision of how the proposed tools, platforms, approaches, methods, and biological applications relate to one another in the context of toolkits and the relative target dates for their interactions;
• The rationale for inclusion of partnerships (e.g., industrial, foundations) outside of the CCBIR Center, if any; and
• A description of how the proposed CCBIR Center addresses imaging needs and opportunities in the broader basic cancer biology research community.

Letters of Support: Include letters of support as appropriate.

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.
• Detailed Resource Sharing Plans for sharing of intellectual and technological resources is a fundamental aspect of the CCBIR Program. Resource Sharing Plans should be described here, while referring to the salient ACC 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; 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.

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Core: Administration and Coordination Core
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

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

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

Project Summary/Abstract: Provide overall goals/abstract/summary for the Administrative Core.

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

List all performance sites that apply to the specific component.

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

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

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

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

Specific Aims: Succinctly describe the list of specific objectives and goals of the Administrative Coordination Core.

Research Strategy:

This section will describe the Administration and Coordination Core (ACC) and should include the following subheadings: Organizational Structure and Staff Responsibilities; External Advisory Panel (EAP); and Center Outcomes Vision.

Organizational Structure and Staff Responsibilities:

• Describe and justify the overall structure of the CCBIR Center and how the PD(s)/PI(s) and the proposed staff will be organized with respect to the ACC, TECH, and RTB units and their primary functions;
• Indicate the relationship of the ACC to the administrative structure of the applicant institution and partnering institutions, if any. It should not be presumed that the best way to organize the CCBIR Center is division along existing institutional boundaries, or the prior research activities of the individual PD(s)/PI(s);
• Describe the strategies that will be implemented to increase representation and career enhancement of underrepresented minorities in the biomedical research workforce who will participate in the Center’s research program;
• Describe plans for partnering with a cancer research advocate (or patient advocate) to engage and participate in Center activities, including but not limited to the Program Steering Committee, and Annual Meetings and scientific outreach (for a description on research advocacy, visit: https://www.cancer.gov/about-nci/organization/oar/research-advocacy);
• Describe the structural and procedural elements governed by the ACC leadership that will ensure the respective TECH and RTB Units function to create integration, iteration, and synergy;
• Describe criteria and processes by which CCBIR Center members are acknowledged in publications resulting from CCBIR projects and how the ACC mediates disputes should they arise;
• Describe in this section how the ACC will manage respective Resource Sharing Plans required under NIH policy.

External Advisory Panel (EAP):

• After the award is issued, each CCBIR Center must form an EAP consisting of two co-Chairpersons who, together, have expertise in the cancer biology and imaging technology areas being pursued by the Center;
• Potential EAP members MUST NOT be contacted or appointed prior to completion of the application submission and review, and should not be named in the application;
• Describe the size of the EAP and scientific disciplines of anticipated panel members that would be represented on the EAP.

Vision Statement of Center Outcomes: This section of the application should entail forward-looking statements about the CCBIR Center's potential impact beyond the initial award period, addressing all the aspects identified below.

• Describe how anticipated achievements in the performance period would be leveraged to continue major advances in basic and/or pre-clinical cancer biology research with national impact;
• Describe plans to facilitate access and broader adoption of technologies developed within the CCBIR Center award period through academic and/or industrial partnerships;
• Describe how the CCBIR Center would transition technological and conceptual innovation into future projects and programs (e.g., Program Project Grants, SBIR);
• Describe the metrics for determining success during the CCBIR award period and how unanticipated obstacles to the plan may be overcome.

Letters of Support: Include letters of support as appropriate.

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.

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

When preparing your application, use Component Type TECH.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

Project Summary/Abstract: Provide overall goals/abstract/summary for the TECH.

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of TECH Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

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

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

Specific Aims: Describe the specific objectives and goals of the TECH Unit.

Research Strategy:

This section of the application should address the background and salient approaches and methods in the TECH Unit with enough detail for critical evaluation of both the quality of the research activities and how they contribute to the CCBIR Center Theme.

Applicants should use the standard structure of the Research Strategy section (i.e., sub-sections Significance, Innovation, and Approach).

Within these sub-sections, address the following additional aspects of the TECH Unit:

Describe the rationale for the proposed technologies and how they relate to development of a specific imaging toolkit(s) in the context-of-use for a cancer biology research problem(s);

Describe, as appropriate, complementary technologies or approaches supporting a goal of interoperability, and ability of the imaging toolkits to be responsive to the emerging needs of cancer biologists in solving problems related to the Center Theme;

Detail the process to pursue alternative approaches to solving technological problems in development of the toolkit(s) if the main conceptual thrust should prove unfeasible within the TECH Unit or through iteration with the RTB Unit.

Letters of Support: Include letters of support as appropriate.

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.

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.

When preparing your application, use Component Type RTB.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Research Test-Bed Unit
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

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

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

Project Summary/Abstract: Provide overall goals/abstract/summary for the RTB.

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of RTB Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

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

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

Specific Aims: Describe the specific objectives and goals of the RTB Unit.

Research Strategy: This section of the application should address the research directions in the RTB Unit with enough detail for critical evaluation of the cancer cell biology question(s) in the context of the CCBIR Center Theme.

Applicants should use the standard structure of the Research Strategy section (i.e., sub-sections Significance, Innovation, and Approach).

Within these sub-sections, address the following additional aspects of the RTB Unit:

• Explain how the RTB lines of investigation present an opportunity to demonstrate and optimize the imaging toolkit(s) under development;
• Describe plans for RTB Unit personnel to work with the TECH Unit and engage in iterative experimentation and feedback;
• Explain the RTB Unit's process for evaluating success versus potential failures at different stages of the award period and the role of the RTB Unit in addressing, as appropriate, such aspects as the availability of new technologies, sample requirements, and experimental conditions under development;
• Detail the process by which the RTB Unit will turn over toolkit demonstration activities to the TECH Unit when iterating between technology development and cancer biology inquiry;
• Describe the overarching process by which toolkits are evolved in experimental complexity as parameters are clarified after advanced iterative cycles between TECH and RTB units in the latter stages of the CCBIR Center;
• Describe how the RTB Unit plans to demonstrate integration of toolkit constituents, which may begin as parallel research activities, into an interoperable system where applicable.

Letters of Support: Include letters of support as appropriate.

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.

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

For this particular announcement, note the following:

A meritorious CCBIR Center application is expected to be well-balanced in multidisciplinary science that spans expertise in both cellular imaging technology development and cancer biology research. The overarching goal of the CCBIR Program is to support a cadre of Centers with national impact that are at the forefront of developing extracellular to cellular and subcellular scaled imaging technologies and collectively have transformative potential to impact fundamental challenges in cancer research. Meritorious applications are anticipated to articulate how the interactions between TECH and RTB Units produce uniquely enabling cellular imaging resources that advance our fundamental understanding of cancer biology processes.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CCBIR Center as a whole 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 Center proposed).

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

Does the CCBIR Center 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 CCBIR Center 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: How likely are the imaging technologies and approaches proposed for development into toolkits by the CCBIR Center to become an important resource for cancer biology researchers? What is the potential for wider adoption of technical or conceptual innovation developed by the CCBIR Center in the long-term?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the CCBIR Center? 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 to this FOA: How well does the proposed CCBIR Center utilize combined expertise in both imaging technology and cancer biology research? How well-recognized are the applicant PD(s)/PI(s) as leaders in their respective fields with experience in managing multidisciplinary teams?

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 to this FOA: How well does proposed study uniquely combine imaging and allied technologies in a manner that is enabling for the Center's cancer research Theme?

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

If the CCBIR Center 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?

Specific to this FOA: How well does the application justify the rationale and motivation for selection of the tools and integrated toolkit(s) to address the basic cancer biology research challenge(s) that defines the CCBIR Center Theme? What is the potential for synergy in how the Center plans to iteratively relate the TECH and RTB Units?

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: What are the applicant institution(s)' existing technology development infrastructure, resources, or cores and how well can they be leveraged to complement the proposed CCBIR Center? How well would the existing or proposed external partnerships through foundations or industry extend the resources for the CCBIR Center? How well does the environment facilitate multidisciplinary relationships and the iterative flow between the TECH and RTB units?

As applicable for the CCBIR Center 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.

Review Criteria - Overall

Integration

Will the proposed CCBIR Center be a truly integrated entity, rather than a collection of unrelated units? How well does the CCBIR Center organization promote scientific, technical, and administrative integration, synergy and a cohesive research program? How well do the applicants describe the plans for collaboration and sharing of models, software, and other resources within the CCBIR Center and across the Network? Do the overall research theme and the proposed components (ACC, TECH, RTB) require a Center-based research structure for success? How integrated are the individual components to form a CCBIR Center that is greater than the sum of its parts?

Reviewers will consider each of the review criteria outlined below to assess the scientific merit of the ACC but will give only one adjectival rating for the entire Core (criterion scoring is not used for this component).

• How appropriate is the expertise of the ACC team to manage logistics and communication within the CCBIR Center?
• How clear are the strategies for increasing representation and career enhancement of underrepresented minorities in the biomedical research workforce?
• How reasonable and achievable is the plan for partnering with a cancer research advocate?
• How effective is the plan for ensuring the TECH and RTB Units function to create integration, iteration, and synergy?
• How appropriate are the anticipated scope of expertise and processes for oversight and strategic planning of the External Advisory Panel? How well will they address the needs of the proposed CCBIR Center?
• How well does the Vision Statement describe: How CCBIR Center achievements would be leveraged to continue advances in basic and/or pre-clinical cancer biology research with national impact; Plans to facilitate access and broader adoption of CCBIR Center technologies through academic and/or industrial partnerships; How the CCBIR Center would transition technological and conceptual innovation into future projects and programs; Metrics for determining success during the CCBIR award period and how unanticipated obstacles to the plan may be overcome?

Reviewers will consider each of the review criteria outlined below to assess the scientific merit of the TECH Unit but will give only one adjectival rating for the entire Unit (criterion scoring is not used for this component). The TECH Unit does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a TECH Unit that by its nature is not innovative may be essential to advance a field.

Significance

• How well does the TECH Unit provide rationale for the proposed technologies and how they relate to development of a specific imaging toolkit(s) in the context-of-use for a cancer biology research problem(s)? How rigorous is the prior research that supports the proposed TECH Unit? How well does the TECH Unit advance the overall research theme of the CCBIR Center?

Investigator(s)

• How well-suited are the Project Lead(s), collaborators, and other researchers for the TECH Unit? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If the TECH Unit is collaborative or has multi-Unit Leads, how complementary and integrated is the expertise of the investigators? How optimal is the use of the combined TECH Unit multidisciplinary research expertise? How does the TECH Unit benefit from the unique scientific expertise of the CCBIR Center?

Innovation

• How unique and potentially transformative are the proposed TECH Unit tools that collectively, as an integrated toolkit, offer promise to open new directions in research on the fundamental problem(s) underlying the Center's Theme? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, models, or interventions proposed?

Approach

• How well-reasoned and appropriate are the overall strategy, methodology, and analyses to accomplish the specific aims of the TECH Unit? Have investigators included plans to address weaknesses in the rigor of prior research that serves for supporting the TECH Unit? How robust and unbiased is the proposed approach? 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? How adequate is the level of detail for the process of pursuing alternative approaches for solving technological problems in development of the toolkit(s)?
• If the TECH Unit involves human subjects and/or NIH-defined clinical research, how justified are the plans in terms of the scientific goals and research strategy proposed 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)?

Environment

• How well does the TECH Unit environment promote collaborations and multidisciplinary research? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Unit? How will the TECH Unit benefit from unique features of the scientific environment of the CCBIR Center, subject populations, or collaborative arrangements?

Reviewers will consider each of the review criteria below in the determination of scientific merit but will give only one adjectival rating for the entire RTB Unit (criterion scoring is not used for this component). The RTB Unit does not need to be strong in all categories to be judged likely to have major scientific impact. For example, an RTB Unit that by its nature is not innovative may be essential to advance a field.

Significance

• How well does the RTB Unit explain how the RTB lines of investigation present an opportunity to demonstrate and optimize the imaging toolkit(s) under development? How rigorous is the prior research that serves as the key support for the proposed RTB Unit? How well does the RTB Unit advance the overall research theme of the CCBIR Center?

Investigator(s)

• How well-suited are the Project Lead(s), collaborators, and other researchers well suited to the RTB Unit? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If the RTB Unit is collaborative or has multi-Unit Leads, how complementary and integrated are the expertise of the investigators? How optimal is the use of the combined RTB Unit multidisciplinary research expertise? How does the RTB Unit benefit from the unique scientific expertise of the CCBIR Center?

Innovation

• How unique and potentially transformative are the proposed RTB Unit tools that collectively, as an integrated toolkit, offer promise to open new directions in research on the fundamental problem(s) underlying the Center's Theme? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, models, or interventions proposed?

Approach

How well-reasoned and appropriate are the overall strategy, methodology, and analyses to accomplish the specific aims of the RTB Unit? How reasonable are the plans for RTB Unit personnel to work with the TECH Unit and engage in iterative experimentation and feedback? How satisfactory is the RTB Unit's process for evaluating success versus potential failures? How clear is the process by which the RTB Unit will turn over toolkit demonstration activities to the TECH Unit when iterating between technology development and cancer biology inquiry? Is the overarching process for toolkit evolution described clearly whereby the RTB and TECH Units iteratively cycle to account for experimental complexity? How adequately described are the plans for the RTB Unit to demonstrate integration of toolkit constituents into an interoperable system?

• If the RTB Unit involves human subjects and/or NIH-defined clinical research, how justified are the plans in terms of the scientific goals and research strategy proposed 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)?

Environment

How well does the RTB Unit environment promote collaborations and multidisciplinary research? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Unit? How will the RTB Unit benefit from unique features of the scientific environment of the CCBIR Center, subject populations, or collaborative arrangements?

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

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

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

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

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

Not Applicable

Not Applicable

Not Applicable

As applicable for the CCBIR Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

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

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

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

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

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

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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.

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

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

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

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

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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 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) 2 CFR Part 200 Administrative Regulations, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, NIH Grants Policy Statement (which implements the aforementioned HHS Regulations (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 primary responsibility for:

The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the CCBIR Center in accordance with these terms and conditions of the award.

Specific PD(s)/PI(s) responsibilities and rights will be to:

• Oversee research activities including defining the research objectives, conducting specific studies, analysis and interpretation of research data, preparation of publications, and disseminating approaches, methods, models, software, and tools broadly to the cancer research community;
• Serve on the CCBIR Program Steering Committee. The CCBIR Program PD(s)/PI(s) (contact PD/PI for applications with multiple PD(s)/PI(s)) are required to serve as members of the Steering Committee;
• Work closely with the NCI Program Director or Project Scientist (see below) on the coordination and management of CCBIR Program activities. These actions involve (but will not be limited to) participation in annual CCBIR Program investigators' meetings, working groups, and teleconferences with NCI scientific and program staff and other awarded investigators, as needed;
• Adhering to the policies and recommendations of the CCBIR Steering Committee to the extent consistent with applicable grant regulations; and
• Ensure that data are shared as appropriate and in accordance with the data sharing plan and NCI data sharing policies.

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:

One or more designated NCI Program staff members will have substantial involvement as Project Scientist(s).

The specific roles of the substantially involved NCI staff members include the following activities:

• Be assigned to each of the awarded CCBIR Centers. This staff member is a scientist who is selected because of relevant scientific content-area expertise and experience with regard to the scientific goals and objectives of a given U54 award. Together, these staff members will have substantial scientific and programmatic involvement through technical assistance, advice, coordination, and collaboration above and beyond the levels required normally for program stewardship of grants, as described below. However, the role of the NCI staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the awardees, and that NCI staff will have the opportunity to offer input into this process.
• Coordinate and facilitate interactions and collaborations among the CCBIR Center awardees and across complementary NCI programs relevant to the CCBIR Program mission.
• Facilitate organization of CCBIR Program annual investigators' meetings, working groups and teleconferences as needed.
• Review progress of CCBIR awardees, conducting periodic site visits, and taking other actions as needed.
• Provide scientific and technical assistance and advice to the awardees as appropriate, serving as scientific collaborators when appropriate.
• Assist in avoiding unwarranted duplication efforts with other projects funded within the CCBIR Program.

Additionally, 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.

Areas of Joint Responsibility:

The CCBIR Program Steering Committee will have governance over the CCBIR Program. The NCI Project Scientist and the contact PD/PI of the Cooperative Agreement awards funded under this FOA will be jointly responsible for:

• Serving on the CCBIR Program Steering Committee. The CCBIR Center PD/PI (contact PD/PI for applications with multiple PDs/PIs) is required to serve as a member of the Steering Committee and each CCBIR Center will collectively have one vote. PD/PI may serve as a chairperson of CCBIR Program Steering Committee that will rotate on a timely basis among all PD/PI members. The designated NCI project scientist will serve on the CCBIR Program Steering Committee and has one vote.
• Coordinating the standing schedule for CCBIR Program Steering Committee meetings and face-to-face meetings as needed.
• Defining and monitoring CCBIR Program milestones and annual goals, developing collaborations among the CCBIR Program members as well as with other complementary NCI programs relevant to the CCBIR Program mission.
• Coordinating dissemination of Centers' output to the broader cancer research community.
• Determining areas of shared research interest for the CCBIR Program, development of research priorities and collaborative opportunities, in order to further the goals of the CCBIR Program.
• Developing common scientific and administrative policies, guidelines, and procedures, best practices including optimization of specific CCBIR Center research procedures, CCBIR Program best practices, data elements for harmonization, and sharing and dissemination of data, technologies, models, reagents, probes, and resources.

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 Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual 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.

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 agreements are 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.

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: 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

Nastaran Zahir, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6333
Email: nas.zahir@nih.gov

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

Amy Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6375
Email: amy.bartosch@nih.gov

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

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