Part 1. Overview Information

Key Dates

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for U54 Research Centers that will collectively establish the Radiation Oncology-Biology Integration Network (ROBIN). ROBIN U54 Centers will provide highly focused research capabilities that will:

• Prioritize and support research to test translational hypotheses that advance understanding of mechanistic interactions and biologic consequences of radiation treatment;
• Support longitudinal collection of clinically annotated research biospecimens prior to (e.g., baseline), during (e.g., on-treatment), and after radiation therapy;
• Develop a multidisciplinary workforce and engage stakeholders with the expertise to conduct studies in translational and pre-clinical research to best inform clinical radiation oncology studies, including leveraging data science and informatics approaches.

Background

Approximately 50% of cancer patients are treated with radiation during the course of their disease. Since its inception as a cancer treatment over a hundred years ago, radiation therapy has used a technology-focused approach as well as mathematical descriptions of tumor cell and normal tissue biology (based on dose size and fractionation) to determine an optimized methodology. The discoveries over the last 20 years from human genomic research with increasing availability of functional -omics , big data, and molecular tools now used for precision medicine are relatively untapped in radiation oncology. The ROBIN FOA provides an opportunity to apply new biological knowledge in the optimization of radiation treatment and its combination with systemic drugs and other agents. Historically, most radiobiology research has been conducted either in cell lines or in pre-clinical model systems with limited data derived from intact human tumors. Because radiation oncology research is of less interest to the pharmaceutical industry, combination therapy using radiation has not been studied to the same degree as combinations of pharmaceutical agents. Thus, radiation oncology represents a dichotomy where the technical precision of radiation delivery to tumors continues to improve, but the biological determinants of how tumors and normal tissues respond and adapt to radiation therapy over time is far less understood, especially in humans, relative to other forms of cancer therapy. Over time, this has created a knowledge gap and an unmet need to characterize radiation treatment so that the biological basis of patient responses and outcomes can be leveraged to both improve eradication of cancer cells and mitigate toxicity to normal tissues.

Key Requirements of the ROBIN Centers

All proposed ROBIN U54 Research Centers must include the following main components (for additional details on the requirements, please see Section IV Application and Submission Information).

(A) Overall Research Focus. Each proposed Research Center must articulate an overarching scientific theme that defines the Center. All proposed research projects must be planned with clear potential to longitudinally monitor and assess radiation response dynamics in human patients with the goal of developing a holistic understanding of treatment ramifications in the cancer type represented by the Center.

(B) Center Organizational Structure. Each ROBIN Center must be organized as follows:

1. Molecular Characterization Trial. At the foundation of each proposed ROBIN U54 Center is the Molecular Characterization Trial component focused on longitudinal collection of biospecimens and multimodal data from patients prior to-, while on-treatment, and after radiotherapy. It is anticipated that the molecular characterization cohorts will be designed as small N, high-content studies, for example where each patient serves as their own control over the treatment. Applicants must respectively justify Molecular Characterization Trial parameters (e.g., number of subjects, expansion cohorts, data types, sampling requirements) through a Characterization Plan and Statistical Plan (see Section IV Application and Submission Information).

2. Research Projects. Each proposed ROBIN U54 Center must have a minimum of two (2) well-developed and interrelated Research Projects with specific aims that directly mesh with the scope and design of the Molecular Characterization Trial. Research projects must be hypothesis-driven and guided by the specific radiation oncology problem ROBIN Center seeks to address (a Center's "Theme"). Accordingly, the workflow design of proposed ROBIN Centers would ideally be based on iterative cycles hypothesis testing leveraging samples and multimodal data obtained from a small Molecular Characterization Trial cohort, which in turn motivates the next cycle of refinement, experimental optimization, and innovation for advancing hypothesis testing with a subsequent cohort.

3. Cores. Resource Cores provide support and capacities within each ROBIN Center dependent on the research service needs. Examples of Resource Core functions include, but are not limited to: data sciences, imaging, dosimetry, biospecimens, models, -omics, statistics, pathology.

Core requirements for this RFA include at least one Resource Core, one Administrative Core, and one Cross-Training Core. The Cross-Training Core's responsibility is to facilitate scientific cross-pollination between radiation oncology, radiation biology, and medical physics within an individual ROBIN Center and across the network with the broader mission of workforce development across these sectors.

(C) Research Team. Each ROBIN Center must consist of appropriately diversified, interdisciplinary expertise spanning the radiation oncology-biology spectrum consistent with the overarching theme and hypotheses to be tested. Multi-PI applications that uniquely maximize team science approaches and productivity between clinicians, radiation and cancer biologists, medical physicists, and computational scientists towards a common goal over the project period are strongly encouraged.

(D) ROBIN Network. Each ROBIN Center will be collaboratively engaged with other ROBIN Centers to collectively operate as the ROBIN network commensurate with NCI guidance under the Cooperative Agreement funding instrument. Built into this RFA is a restricted fund to support trans-ROBIN collaborative pilot projects. The ROBIN Network is intended to have a national impact and provide leadership for the cancer research community to move towards a new era of personalized radiation oncology where treatment planning may be optimized in new ways based on an individual patient’s unique biological signatures to reliably predict radiation response, overcome treatment failure, and mitigate normal tissue toxicities.

Areas of Scientific Priority and Interests

Priority research project areas consistent with the goals of this FOA include, but are not limited to:

• Factors that demarcate characteristics (e.g., functional -omics), heterogeneity, and mechanistic basis of radiation responses in tumor, proximal normal tissue, and distal organ sites;
• Collection and convergence of data-dense, high-content, multimodal approaches that describe longitudinal (e.g., before, on-treatment, and after) radiation response dynamics, which have the potential to inform treatment planning or trial design;
• Mechanisms of adaptation to radiation treatment that underlie the emergence of adaptive resistance or failure;

The long-term goal of the ROBIN is to catalyze a deeper understanding of radiobiological responses in tumor and human tissues that has the potential to serve as a nucleation point for further development of radiation or combined modality trial concepts through the NCI's Experimental Therapeutics Clinical Trials Network or National Clinical Trials Network.

Cancer Type

Ideally, a successful ROBIN Center would be uniquely positioned to investigate the translational mechanistic consequences of radiation in cancers where the biological basis of treatment responses is understudied, despite radiation being the standard of care. It is anticipated that each ROBIN Center will be specialized to focus on a specific type of cancer as defined by the applicant based on the cell of origin, anatomical location, or specific molecular genotype. Several types of cancer are likely candidates for study in the ROBIN framework. Esophageal, rectal, and sarcoma cases typically have large surgical specimens that could be longitudinally studied at both baselines and through the course of radiation treatment. Small biopsies for oral, pharyngeal, and cervical cancers are often feasible. Biopsies of the brain, lung, or pancreas are more challenging but represent a compelling unmet need for the study to improve treatment outcomes.

Radiation Treatment Modality

In addition to cancer type(s), it is anticipated that a ROBIN Center's "Theme" would be closely intertwined with the treatment modality(ies) studied in relation to the radiation oncology problem the Center seeks to address. The RFA is agnostic to radiation type (e.g., external beam, radionuclide). It is anticipated that radiation treatment is the standard of care for the given patient cohort(s) that constitute the Molecular Characterization Trial component and will include radiation in combination with other agents and modalities. Standard of care is acceptable, but not required. It is anticipated that radiation treatment is the standard of care, or a part thereof, for the given MCT cohort. Radiation dosimetry is expected to play a key role in the design of the Molecular Characterization Trial and interpretation of these data.

Orthogonal Characterization Approaches

It is anticipated that molecular characterization approaches based on tissue procurement from patients over the course of radiation therapy will be accompanied by orthogonal non-invasive approaches (e.g., imaging, circulating markers, sensor technologies). Studies may be complemented by correlative radiation treatment experiments in established pre-clinical models (e.g., canine, Patient Derived Xenografts, Genetically Engineered Mouse Models) that directly support testing the overall hypothesis that guides a respective ROBIN Center. Opportunities exist for available pharmacodynamic molecular characterization assays and function-omics approaches to be incorporated into hypothesis testing in a radiation treatment setting, such as assays with demonstrated sensitivity and specificity to assess dynamic changes in DNA damage and repair, protein phosphorylation, epigenetic states, and/or cell cycle.

Pre-clinical models with demonstrated relevance to the Molecular Characterization Trial design may be leveraged in the initial project period to refine technological innovation and capabilities planned for characterization studies with human patient samples. ROBIN Center applicants must articulate the rationale for utilizing the proposed suite of assessments and will be required to provide a plan that details procedures and type of data to be acquired, assay characteristics, and analytical performance per tissue or specimen type. Procurement and analysis of paired tumor and normal tissue specimens will be encouraged, but not required. The characterization plan will be complemented by a statistical plan that describes the patient cohort design including the basis for the proposed study population size, plan for iteration between research projects and expansion cohorts (if applicable), and expected feasibility to produce interpretable results in pursuit of the radiobiological endpoints the ROBIN Center seeks to study.

Data Science

ROBIN Centers collectively share a mandate to characterize the biological determinants of radiation treatment responses over time. Given the high-content data-intensive nature of this work, it is expected that members of the ROBIN network will adhere to data management and sharing policies developed in conjunction with NCI staff within the Cooperative Agreement environment that facilitate harmonization and interoperability of multiscale data and diverse data types. This will poise ROBIN as a unique contributor of multi-modal data at the intersection of both cancer biology and radiation oncology to the broader National Cancer Data Ecosystem. In leveraging existing data infrastructures, it is anticipated that ROBIN Centers will become increasingly engaged in alliances with other data-intensive programs (e.g., Cancer Systems Biology Consortium, Human Tumor Atlas Network, Acquired Resistance to Therapy Network, NCI-DOE Joint Design of Advanced Computing Solutions for Cancer) as the network matures, creating additional opportunities for collaboration and scientific discovery consistent with the goals of the cancer data ecosystem. For these reasons, it is strongly encouraged that each ROBIN Center have a dedicated Data Management Specialist position as key personnel within the relevant Core.

Trans-ROBIN Collaborative Pilot Projects

• ROBIN Pilot Projects that are collaborative between ROBIN Centers and the broader research community supported through the Restricted Fund are encouraged. ROBIN pilot projects are complementary to ongoing activities in the Molecular Characterization Trial or Research Project components and may incorporate new technologies, probes, computational tools, biological models, and/or biospecimens to test or validate new ideas that fall within the scope of the ROBIN center award research. ROBIN pilot projects may entail support for direct hands-on training in data acquisition and interpretation, didactic or educational outreach activities, which for these purposes would enhance the goals of the Cross-Training Core(s).
• ROBIN Pilot Projects are developed in consultation with, and under the direction of a designated ROBIN Center PI(s) at a minimum on an annual basis. Projects that are exclusive to personnel within a single ROBIN Center are not eligible for Restricted Fund support. Trans-ROBIN Center pilot projects are eligible for Restricted Fund support. The duration of a typical ROBIN Pilot project is one year or less, however, an evolving pilot project may be prioritized to recompete for Restricted Fund support over multiple years.
• Final selection of ROBIN pilot projects supported by the Restricted Fund will be subject to ROBIN Steering Committee approval with NCI Program staff guidance in accord with authority under the Cooperative Agreement mechanism. Issuance of Restricted Fund budget support for approved ROBIN pilot projects will be to the ROBIN Center institution and indirectly to external collaborators through subcontracts from the parent award.

Non-Responsive Applications

The following projects would be considered non-responsive to the ROBIN Center FOA:

• Applications that do not include a molecular characterization cohort of human patients that incorporates longitudinal biospecimen collection prior to-, on-treatment, and after radiotherapy. Based on this, all applications are considered clinical trials even if the treatment proposed is standard of care. Note that combination therapies are anticipated. However, applications are non-responsive if the combination does not include a radiation therapy modality. Standard of care is not a requirement for the MCT component;
• Applications that do not propose an overarching scientific hypothesis that guides the rationale for multi-disciplinary research projects aimed to elucidate relationships between radiation treatment and human radiobiological responses;
• Applications that focus solely on analytical development of biomarkers as well as projects proposing extensive pre-clinical model development;
• Applications that do not propose a Cross-Training Core.

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

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

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

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

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

Applicant organizations

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

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Ms. Julie Hong
National Cancer Institute (NCI)
Telephone: 240-276-5690
Email: [email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

The application should consist of the following components:

• Overall: required; maximum of 1
• Administrative Core: required; maximum of 1
• Molecular Characterization Trial: required; maximum of 1
• Research Project: required; minimum of 2
• Shared Resource Cores: required; maximum of 2
• Cross-Training Core: required; maximum of 1

Overall Component

When preparing your application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

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

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

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

Project/Performance Site Locations (Overall)

Enter primary site only.

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

Research and Related Senior/Key Person Profile (Overall)

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

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

Budget (Overall)

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

Restricted Fund for Collaborative ROBIN Pilot Projects: Enter "Restricted Fund for ROBIN Pilot Projects" under the "Other Expenses" category in the Budget form as the following percentage of direct costs per year: 0% in year 1, a minimum of 15% of direct costs in year 2 through year 5. Refer to the Overall Research Strategy section for more details.

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

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

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Outline the specific aims for the entire ROBIN Center. The Specific Aims in this section of the Research Plan should be overarching and distinct from the aims of the individual research projects. Define the compelling scientific question/challenge(s) in the radiation sciences that the Center as a whole seeks to address.

Research Strategy: Provide an overview of the proposed ROBIN Center. Describe the vision of the ROBIN Center by addressing each of the aspects indicated below:

• The scientific focus in the radiation oncology-biology continuum that defines the ROBIN Center's Theme;
• The rationale for the proposed type(s) of cancer and radiation treatment modality(ies) represented and the specific research challenges faced by patients with those cancers that the Center intends to address;
• The significance of the proposed research in terms of timeliness and potentially transformative outcomes in the context of currently available concepts on the underlying biological responses to radiation treatment;
• The overall philosophy and workflow that will be used to guide the iterative relationship between the Molecular Characterization Trials and Research Projects to make an impact on the research challenge(s) that defines the ROBIN Center's Theme;
• A timeline that illustrates the ROBIN Center's vision of how the proposed Molecular Characterization Trial and Research Project components relate to one another in the context of proposed tools, platforms, approaches, methods, biological, and computational applications and the relative target dates for their interactions where applicable;
• The rationale for inclusion of partnerships (e.g., industrial, foundations) outside of the ROBIN Center, if any; and
• A description of how the proposed ROBIN Center addresses needs and opportunities in the broader radiation sciences research community. Describe the process for how the ROBIN Center will solicit pilot projects proposals from the within the ROBIN Center broader research community in the post-award period (e.g., under coordination of the Administrative Core, Cross-Training Core).

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

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

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The Data Sharing Plan should be provided only in the Overall section and encompasses all the activities of the Center;
• The Data Sharing Plan should briefly describe the types of data and computational resources that are expected to be generated and shared, consistent with achieving the goals of the ROBIN Center. Data Sharing Plans are expected to describe plans for anonymization, annotation, multimodal data integration; harmonization; transfer learning; development of robust statistical-, Artificial Intelligence-, and/or Machine Learning-ready datasets to facilitate formats that are accessible to increase the value of these data for sharing with the scientific community;

Note that NCI Program staff may negotiate modifications to these plans prior to funding. Specifically, applicants will be expected to abide by the policies and procedures for data, software, and computational model sharing within the context of the NCI Cancer Data Ecosystem including infrastructure and resources for access of multi-modal data, elastic computation, and analysis through the Cancer Research Data Commons developed upon availability (see Section VI: Terms and Conditions of Cooperative Agreement).

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application, use Component Type Admin Core.

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

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

Budget (Administrative Core)

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

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

PHS 398 Research Plan (Administrative Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

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

Research Strategy: This section will describe the Administrative Core and should include the following subheadings: Organizational Structure and Staff Responsibilities; and Center Outcomes Vision as follows:

Organizational Structure and Staff Responsibilities:

Describe and justify the overall structure of the ROBIN Center and how the PD(s)/PI(s) and the proposed staff will be organized with respect to the Molecular Characterization Trial, Research Project, and Core components and their primary functions;

• Indicate the relationship of the Administrative Core 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 ROBIN Center is division along existing institutional boundaries or the prior research activities of the individual PD(s)/PI(s);
• Describe the structural and procedural elements governed by the Administrative Core leadership that will ensure the respective components function to create integration, iteration, and synergy both within the ROBIN Center and across the ROBIN network as a whole;
• Describe the strategies that will be implemented to increase representation and career enhancement of women and underrepresented minorities in the 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 ROBIN 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 criteria and processes by which ROBIN Center members are acknowledged in publications resulting from ROBIN projects and how the Administrative Core mediates disputes should they arise;
• Describe in this section how the Administrative Core will manage respective Resource Sharing Plans required under NIH policy.

Vision Statement of Center Outcomes:

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

• Describe the potential for the ROBIN Center findings to serve as a nucleation point for further development of radiation in combined modality trial concepts through the NCI's Experimental Therapeutics Clinical Trials Network or National Clinical Trials Network.
• Describe how anticipated achievements in the performance period have the potential for national impact to strengthen the intersection between basic and clinical cancer research;
• Describe plans to facilitate access and broader adoption of concepts, biomarkers, and/or technologies developed within the ROBIN Center award period through academic and/or industrial partnerships;
• Describe how the ROBIN Center would transition 1) new concepts, 2) technological innovation, and 3) workforce development into future projects and programs (e.g., P01 Program Project Grants, T-32 Training Centers, SBIR spin-off projects);

Describe the milestones and/or metrics for determining success during the ROBIN award period and how unanticipated obstacles to the plan may be overcome.

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

• Resource Sharing Plans should only be included in the Overall component

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Administrative Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Molecular Characterization Trial

When preparing your application, use Component Type Mol Character Trial

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

SF424 (R&R) Cover (Molecular Characterization Trial)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of the Molecular Characterization Trial
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Molecular Characterization Trial)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Molecular Characterization Trial)

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

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

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

Project /Performance Site Location(s) (Molecular Characterization Trial)

• List all performance sites that apply to the Molecular Characterization Trial component.
• There are no limitations placed on the number of Molecular Characterization Trial performance sites, however, justification for performance sites at partnering institutions in addition to the applicant institution must be articulated in the Research Plan section.

Research & Related Senior/Key Person Profile (Molecular Characterization Trial)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• The Project Lead must dedicate at least 1.8 person months effort to the project for the life of the award. If the project has multiple leads, then each must dedicate at least 1.2 person months effort to the project for the life of the award.
• 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.
• For projects with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other(Specify)' and designate the role under 'Other Project Role Category' as "Project Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Project Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Molecular Characterization Trial)

Budget forms appropriate for each individual research project should be included in the application package. The Project Lead must dedicate 1.8 person months effort to the project for the life of the award. If the project has multiple leads, then each lead must dedicate at least 1.2 person months effort to the project for the life of the award.

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

PHS 398 Research Plan (Molecular Characterization Trial)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the goals of the proposed Molecular Characterization Trial.

Research Strategy: Applicants should use the standard structure of the Research Strategy section (i.e sub-sections Significance, Innovation, Approach). The foundation of a ROBIN Center is the Molecular Characterization Trial component, of which the Research Projects and Cores are dependent. It is anticipated that the design of a ROBIN Center's Molecular Characterization Trial component will have the following features:

• Small cohort size;
• Treatment for the chosen cancer type(s) must include radiation therapy. Standard of care treatment is acceptable but not required;
• Longitudinal sampling (e.g., baseline, on-treatment, post-treatment);
• Multimodal characterization that comprises both invasive and non-invasive approaches (e.g., tumor biopsy, imaging, blood sampling, external sensors/wearables, patient-reported outcomes);

Address the following additional aspects:

• Describe the rationale for the cancer type(s) and treatment approaches represented in the proposed Molecular Characterization Trial component in the context of solving challenges related to the Center's Theme;
• Describe how the proposed suite of orthogonal and/or complementary technologies, assessments, and approaches has potential to provide a holistic view of a patient responses to radiation therapy;
• Describe, if applicable, how the findings from Research Projects may inform iteration and refinement in the design of the Molecular Characterization Trial component through use of multiple cohorts over the ROBIN Center award period;
• Detail the process to pursue alternative approaches in if the main technological or conceptual thrust of the Center should prove unfeasible within the context of the Molecular Characterization Trial.

The Research Strategy must include the following additional sub-sections:

Characterization Plan.

• Detail procedures, assessments, and types of data to be acquired, assay characteristics, and analytical performance per tissue or specimen type. Use of a table listing sample requirements for biospecimens and use of a timeline to illustrate these data with respect to the anticipated (standard-of-care) treatment regime for the proposed longitudinal Molecular Characterization Trial(s) are suggested. Procurement and analysis of paired tumor and normal tissue specimens are encouraged, but not required. The Characterization Plan must detail strategies for inter-site specimen procurement and special handling; inter-relationships of diverse biospecimens and data types; and rigor and reproducibility both within a ROBIN Center or across multiple performance sites at partnering institutions, where applicable.

Statistical Plan.

• Describe the patient cohort design including the basis for the proposed study population size, plan for iteration between Research Projects and expansion cohorts (if applicable). Describe the basis for evaluating heterogeneity (intra- and inter-patient) and changes (dynamics) with respect to time and/or anatomical location(s). Provide justification for Molecular Characterization Trial performance sites in addition to the applicant institution (if applicable), statement of rigor and reproducibility, and expected feasibility to produce interpretable results in pursuit of the radiobiological endpoints the ROBIN Center seeks to study. Note that given the "small N, data dense" nature of the Molecular Characterization Trial component, it is expected that emphasis will be placed on multimodal data (e.g., the frequency of sample collection and number of sample types), as opposed to the overall number of subjects.

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 (Molecular Characterization Trial)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Research Projects

When preparing your application, use Component Type Research Project.

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

SF424 (R&R) Cover (Research Projects)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

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

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

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

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

List all performance sites that apply to each specific Research Project component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• The Project Lead must dedicate at least 1.8 person months effort to the project for the life of the award. If the project has multiple leads, then each must dedicate at least 1.2 person months effort to the project for the life of the award.
• 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.
• For projects with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other(Specify)' and designate the role under 'Other Project Role Category' as "Project Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Project Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Research Projects)

Budget forms appropriate for each individual research project should be included in the application package. The Project Lead must dedicate 1.8 person months effort to the project for the life of the award. If the project has multiple leads, then each lead must dedicate at least 1.2 person months effort to the project for the life of the award.

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

PHS 398 Research Plan (Research Projects)

Each ROBIN Center is required to have a minimum of two Research Projects.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

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

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

Within these sub-sections, address the following additional aspects for each individual Research Project:

• Describe how the hypothesis being tested addresses a challenge in determining the biological basis of response to radiation treatment, its relationship to other proposed Research Projects within the ROBIN Center, and the overall theme of ROBIN Center as a whole;
• Describe the relationship of the proposed Research Project to the Molecular Characterization Trial component of the ROBIN Center. While Research Project studies may be complemented by correlative radiation treatment experiments in established pre-clinical models, a high level of integration and iteration with the Molecular Characterization Trial is expected. Pre-clinical models with demonstrated relevance to radiation treatment may be leveraged in the initial project period to refine technological innovation and capabilities planned for characterization studies with patient samples;
• Describe strategies in the design of the Research Project to distinguish or discern signals, responses, and patterns elicited by radiation relative to other treatments in a combined modality setting;
• If the research project will use a Shared Resource Core, describe how the Core capabilities support the proposed project.

PHS Human Subjects and Clinical Trials Information (Research Project)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Shared Resource Core

When preparing your application, use Component Type Shared Resource Core.

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

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

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Shared Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Shared Resource Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of 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.
• For Cores with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Shared Resource Core)

Budget forms appropriate for each individual research project should be included in the application package.

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

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

PHS 398 Research Plan (Shared Resource Core)

Shared Resource Cores provide support and capacities dependent on the research service needs of the ROBIN Center. Examples of Shared Resource Core functions include, but are not limited to: data sciences, imaging, dosimetry, biospecimens, models, -omics, statistics, pathology. ROBIN Centers collectively share a mandate to characterize the biological determinants of radiation treatment responses over time. Given the high-content data-intensive nature of this work, it is strongly encouraged that each ROBIN Center have a dedicated Data Resource Manager within the Shared Resource Core framework to facilitate workflows, harmonization, and interoperability of multiscale data and diverse data types.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Outline the specific aims of each Shared Resource Core.

Research Strategy: For each Shared Resource Core, the relationship to the Molecular Characterization Trial and Research Project components being supported through the services and/or resources must be described. Address the following additional aspects of each Shared Resource Core:

• Describe integration between each Shared Resource Core and the Molecular Characterization Trial and Research Project components of the ROBIN Center;
• If applicable, detail what Shared Resource Core space, personnel, resources, and/or functions are dedicated to a ROBIN Center where an existing infrastructure or core at the applicant institution or partnering institutions is proposed to be leveraged. Any proposed new shared resources must not duplicate analogous resources already established in the applicant institutions. If existing cores and resources are to be used, then funding to augment such existing resources may be requested. Description of how work related to the Center will be prioritized within such a core must be provided.

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

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

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

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Cross-Training Core

When preparing your application, use Component Type Cross-Train Core.

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

SF424 (R&R) Cover (Cross-Training Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Cross-Training Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Cross-Training Core)

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

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

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

Project /Performance Site Location(s) (Cross-Training Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Cross-Training Core)

• 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.
• For Cores with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field.

Budget (Cross-Training Core)

Budget forms appropriate for each individual research project should be included in the application package.

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

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

PHS 398 Research Plan (Cross-Training Core)

A requirement of this RFA is the establishment of a Cross-Training Core within each ROBIN Center. The Cross-Training Core is intended to foster a culture of scientific cross-pollination between radiation oncology, radiation biology, and medical physics within an individual ROBIN Center and across the network. It is anticipated that Cross-Training Cores develop and sustain a collaborative environment that is mutually beneficial to members of the respective ROBIN Centers to learn, share, and adopt concepts and approaches from each other, which ultimately serves to establish and accelerate a broad range of advances for the field from both a training and expertise perspective, as well adoption of findings that have potential to improve patient outcomes.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Outline the specific aims of the Cross-Training Core.

Research Strategy: Describe the activities of the Cross-Training Core. Cross-Training Core activities may include, but are not limited to: management of ROBIN Center seminars series, generation of didactic materials, facilitation of intra- and inter-Center training opportunities, and coordination of Center and Network scientific meetings; as well as outreach with other stakeholder programs. Address the following additional aspects of the Cross-Training Cores:

• Describe the overall vision or philosophy of the Cross-Training Core in the context of enhancing team science and workforce development for the radiation sciences field;
• Describe plans to integrate or transition the Cross-Training Core with other workforce development efforts (e.g., development of a T-32 Training Program);
• Describe outreach and engagement activities of the Cross-Training Core with other stakeholder constituencies in the cancer research community (e.g., foundations, societies).

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

PHS Human Subjects and Clinical Trials Information (Cross-Training Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Post Submission Materials

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

Section V. Application Review Information

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

For this FOA, note the following:

Reviewers will provide an overall impact score for the entire ROBIN Center (Overall component) and adjectival ratings for individual components except for the Research Projects. For the evaluation of the entire Center (Overall), the Molecular Characterization Trial, Research Projects, and Cross-Training Core will be assessed as the scientific basis of the Center, with the other components enhancing and integrating the overall research program. The overall Impact Score will reflect the synergy and integration across the Center, especially integration between the required basic/mechanistic and preclinical/translational aspects.

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

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

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

Significance

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

Specific to this FOA:

How compelling is the justification for the Center’s research theme and the overall significance of the program of research in terms of potential to improve comprehensive understanding of the biological basis of human patient responses to radiation therapy, clinical trial design, and/or patient outcomes?

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

Investigator(s)

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

Specific to this FOA:

How well does the ROBIN Center combine/integrate/maximize team science productivity between clinicians, radiation and cancer biologists, medical physicists, and computational scientists towards a common goal over the project period?

What is the potential for synergy to develop between clinical, basic biomedical, and physical sciences researchers?

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

Innovation

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

Specific to this FOA:

How well does the proposed ROBIN Center uniquely innovate in ways to integrate-iterate across the Molecular Characterization Trial, Research Projects, and Cross-Training Core?

How novel are research methods aimed at developing multimodal and/or multiscale perspectives in the biological underpinnings of responses in patients who undergo radiation treatment?

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

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

To what extent does the design of the proposed ROBIN Center involve hypothesis-driven approaches that address challenges at the intersection of radiation oncology, cancer biology, and medical physics?

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

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

Specific to this FOA:

How well does the scientific environment at the participating sites stimulate trans-disciplinary research collaborations? How well does the environment facilitate multidisciplinary relationships and an iterative flow between respective teams of researchers?

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

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

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

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

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

Study Timeline

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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 (GDS).

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

Scored Review Criteria - Cores and Research Projects

Review Criteria - Administrative Core

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

• How clearly is the operational structure described including management and communication plans to facilitate (a) achievement of the overall goals of the ROBIN Center; (b) integration across the key components of the ROBIN Center; and (c) interdisciplinary collaborative capabilities?
• To what extent will the evaluation plan be useful for iteratively refining the ROBIN Center’s ongoing activities, informing plans for future collaborative research, and assessing the Center’s impact on the radiation research field?
• For the proposed restricted fund pilot projects, does the applicant propose a detailed process for identifying, evaluating, and selecting high-value and collaborative pilot projects?

Review Criteria - Molecular Characterization Trial

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

Significance

• What is the potential for the design or approaches with successful completion of the aims to improve the radiation oncology field and/or the broader medical oncology field?
• How well does the Molecular Characterization Trial poise the field for feasibility in new precision radiation oncology concepts?

Investigator(s)

• How well does the range of experience and disciplines of the clinical investigative team correspond with the ability to facilitate research and integration across the key components of the ROBIN Center?

Innovation

How well does the application challenge and/or seek to shift clinical practice paradigms by utilizing novel approaches or methodologies, or instrumentation to characterize patient responses to treatment in either time or space?

Approach

• How well do the proposed assessments provide a multimodal and orthogonal perspective of radiation response dynamics and align with the challenge that defines the Center?
• To what extent do the proposed approaches address contextualizing or distinguishing (where appropriate) radiation responses from others in a combined modality treatment setting?
• How will the proposed research designs maximize the reliability and replicability of the findings?

Environment

• How well do the institutional support, equipment and other physical resources available to the investigators enable the proposed project? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Review Criteria - Research Projects

Reviewers will provide an overall impact score for the 'Research Projects' and will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each Research Project.

Significance

• To what extent do the chosen cancer type(s) and research question represent an important challenge or critical barrier to progress in the radiation oncology field?
• How well do the Research Projects address a crucial knowledge gap in the biological determinants of how tumors and normal tissues (where applicable) respond and adapt to radiation therapy over time?

Investigator(s)

• What is the potential for synergy to develop between the Research Project team and other key components of the ROBIN Center?

Innovation

• How well does the Research Project bring novel scientific concepts, technologies, approaches, methodologies, or instrumentation to bear on understanding the biological basis of patient responses to treatment? Note that techniques and approaches used in other fields may be viewed as innovation when uniquely leveraged in the context of the Research Project's hypothesis and ROBIN Center's focus.

Approach

• How well does the Research Project utilize or leverage samples, data, and concepts derived from the Molecular Characterization Trial component to test a hypothesis?
• To what extent does the design of the Research Project contextualize or distinguish (where appropriate) radiation responses from others in a combined modality treatment setting?
• How well does the proposed Research Project design integrate with the other key components of the ROBIN Center to provide a holistic understanding of the biological basis for patient responses to treatment over time?

Environment

• How well does the scientific environment contribute to the probability of success?

Review Criteria - Shared Resource and Cross-Training Cores

Reviewers will provide only one overall adjectival rating for the Shared Resource and Cross-Training Cores (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of the application:

• How well matched is the proposed Shared Resource Core to the needs of the overall ROBIN Center?
• To what extent will the Cores facilitate research via centralized functions and services?
• How likely is it that the Cross-Training Core will impact workforce development for the ROBIN Center and across the ROBIN network as a whole?

Additional Review Criteria - Cores and Research Project

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

Study Timeline

Specific to applications involving clinical trials

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not applicable

Revisions

Not applicable

Additional Review Considerations - Cores and Research Project

As applicable for the Cores and Projects 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 adjectival rating.

Applications from Foreign Organizations

Not applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

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

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

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

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

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

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

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

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

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

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

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

Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution's specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

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

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

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

• Participate in the annual or biannual ROBIN Steering Committee meeting, periodic conference calls and collaborative ROBIN activities.
• Participate in the development of various topical scientific interest groups;
• Identify and promote opportunities for ROBIN research and coordination, including collaborative pilot projects and validation of experimental concepts and observations.
• Identify and promote trans-ROBIN and external collaborations to advance research at the intersection between radiation biology, radiation oncology, medical physics, and computational data sciences.
• Abide by the governance of the ROBIN Center, and all program policies agreed upon by the ROBIN Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations.
• Report progress to the NCI Program Officials on all ROBIN-related research and activities annually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by NCI program staff members on a semi-annual basis.
• Ensure that data are deposited in a timely manner and that models, software, and other tools and resources developed as part of this ROBIN Center are made available according to the Data Sharing Plan and NCI Cancer Data Ecosystem policies and procedures,.
• Ensure that the results of the Research Projects are published in a timely manner.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Participating ROBIN Center members are also encouraged to organize and participate in other Network meetings and workshops, organize collaborative activities, and promote Trans-Network collaborations, and organize and participate in scientific and programmatic working groups.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The specific roles of the substantially involved NCI staff members include the following activities:

• Serve as NCI lead Project Scientists and voting members of the ROBIN Steering Committee;
• Serve as resource for ROBIN Centers and the network as a whole in promoting interactions with other ongoing NCI activities that may be relevant to the goals of the ROBIN Program;
• Assist in avoiding unwarranted duplications of effort across the ROBIN Program;
• Facilitate collaborative research efforts that involve multiple ROBIN Research Centers.
• Evaluate the effectiveness and facilitate Program-wide adoption of resource practices;
• Monitor operations and conduct programmatic evaluations through site visits;
• Make recommendations on overall project directions;
• Make funding decisions on collaborative pilot projects supported through the ROBIN Center restricted funds;
• Reviewing the progress of activities shared among the ROBIN Centers;
• Participate in organizing ROBIN meetings, specialized workshops, and webinars;
• Additionally, an agency program official or IC program director will be responsible for the standard scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

ROBIN will have a Steering Committee as a governing body. The ROBIN Steering Committee will consist of the following voting members:

• The PDsPI(s) of each awarded ROBIN Center (or senior investigator as proxy when applicable) will collectively have one vote; and
• The NCI Project Scientists collectively have one vote for the NCI.

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

Two PD(s)/PI(s), representing two different ROBIN Centers, will be selected to serve as co-chairs of the Steering Committee on a rotating basis following award issuance. All ROBIN Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The Steering Committee may have additional non-voting members.

The ROBIN Steering Committee will meet annually or biannually at the ROBIN Annual Steering Committee Meeting and as needed through monthly virtual meetings. The ROBIN Steering Committee will:

• Identify scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and develop recommendations to NIH/NCI Program Officials for addressing such issues;
• Establish, as necessary, subcommittees to ensure progress of the individual ROBIN Centers, projects, and the network;
• Review the potential of shared support infrastructure(s) at individual ROBIN Centers to serve the needs of other ROBIN Centers and the entire program;
• Develop procedures for soliciting and evaluating ideas for pilot project across the ROBIN as well as criteria for their prioritization and approval;
• Ensure that the ROBIN Centers take advantage of existing NCI and NIH resources and programs;
• Participate in the development of the agenda for the annual or biannual Steering Committee meeting to present scientific progress and future plans from ROBIN investigators; and
• Coordinate dissemination of Network output to the broader cancer research community.

Dispute Resolution:

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

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

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

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

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

Section VII. Agency Contacts

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

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

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

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

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

Michael Graham Espey, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7619
Email: [email protected]

Jeffrey Buchsbaum, M.D., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5690
Email: [email protected]

Bhadrasain (Vik) Vikram, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-5690
Email: [email protected]

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

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.