Required Application Instructions

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

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

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

The purpose of this Funding Opportunity Announcement (FOA) is to encourage research projects addressing challenging cancer problems using systems biology approaches. In support of this goal, the National Cancer Institute (NCI) has initiated the Cancer Systems Biology Consortium (CSBC) through multiple FOAs. The CSBC network will consist of specialized U01 Research Projects (supported under this FOA), U54 CSBC Research Centers (supported under RFA-CA-15-014), and a U24 Coordinating Center (supported under RFA-CA-15-015).

CSBC Research Projects should address a well-defined, discrete, and circumscribed research question in cancer incorporating quantitative experimentation, analysis, modeling and validation, which are the hallmarks of systems biology. As part of the CSBC, investigators from the Research Projects will have the opportunity to share resources and expertise across the Consortium and participate in Consortium activities and annual meetings.

Research strategies that can integrate across molecular, genetic, and cellular events are required to understand the multivariate nature of cancer and to predict tumor behaviors, efficient treatment opportunities, and, ultimately, patient outcome. Cancer systems biology approaches provide the iterative experimental and analytical toolkit necessary for addressing complex problems in cancer research. Through development of measurement technologies, generation of rich datasets, and employment of computational, mathematical, and algorithmic tools, cancer systems biologists have made important strides in describing cancers as integrated systems of genes, networks, and intercellular interactions. Cancer systems biology is uniquely poised to address various important and/or emerging questions in cancer research that would be difficult, if not impossible, to explore fully using other, less comprehensive approaches.

Along with general cancer-related topics such as the heterogeneous nature of tumors and the widely variable genetic underpinnings of cancer, there are a variety of emerging directions in cancer research that are particularly amenable to a systems approach: (a) decoding dynamic tumor-stroma and/or tumor-immune system interactions; (b) integrating chemical, molecular, structural, network, and localization information across temporal and spatial scales to understand tumor behavior; (c) understanding how individual cell states shape the behavior of tumors and tumor ecosystems; (d) determining how the microbiome affects tumor initiation, progression or treatment; (e) forward engineering of cancer systems through the convergence of synthetic biology and systems biology; (f) bridging the many cancer hierarchies; and (g) utilizing cancer systems biology predictions to inform clinical trial design.

In addition to addressing specific biological hypotheses, the continued success of cancer systems biology depends on the development of new methodologies to address complex and multivariate questions, including new theoretical, mathematical and computational techniques, multi-scale modeling approaches capable of integrating across scales from the molecular to the population level, and new biological tools and systems for informing and testing cancer systems biology generated hypotheses.

The CSBC initiative is intended to promote further development of the field of cancer systems biology. The CSBC is designed to foster collaborations between cancer systems biologists and those in other communities, such as cancer biology and oncology, immunology, synthetic biology and population science.

CSBC overall organization: The CSBC will consist of U54 CSBC Research Centers (RFA-CA-15-014), U01 CSBC Research Projects (encouraged under this FOA), and a U24 Coordinating Center (RFA-CA-15-015) that will coordinate activities between the CSBC and a related program, the Physical Sciences in Oncology Network (PS-ON). All parts will be governed by the CSBC Steering Committee with representatives from the funded CSBC Research Centers and Research Projects, the CSBC/PS-ON Coordinating Center and NCI Program staff. Applicants are encouraged to read RFA-CA-15-015 for more information regarding the role of the CSBC/PS-ON Coordinating Center. The CSBC will function as a collaborative network allowing Research Centers and Projects to cross-test ideas, integrate diverse data sets, and validate (or refute) theoretical, experimental, or clinical models.

Governance of the CSBC: The CSBC program will be governed by the CSBC Steering Committee. This governance extends to CSBC Research Projects (see Section VI: Terms and Conditions of Cooperative Agreement.)

Evaluation of the Program: CSBC awardees (including Research Projects awardees) will be required to participate in an external evaluation process of the CSBC program coordinated by NCI Program Staff (see Section VI: Terms and Conditions of Cooperative Agreement.)

Applicants responding to this FOA should propose only one single, cohesive project that is based upon a systems biology approach to cancer research. This approach should include explicit integration of experimental biology and computational or mathematical modeling to build, test and/or validate hypotheses or ideas.

The following examples list cancer areas that are appropriate for this FOA and poised to benefit from a cancer systems biology approach. Note that the list is non-inclusive and is not meant to restrict the scope of investigator-initiated research topics.

• Dynamics of cell-cell interactions: The reciprocal relationship between cancer cells, the host immune system and the tumor microenvironment evolves during cancer progression. How these dynamic and unstable interactions prevent or drive tumor initiation and progression is not well understood. Projects may focus on predictive and testable hypotheses of how dynamic cell-cell (tumor-tumor, tumor-immune, tumor-stroma, immune-stroma, etc.) communication affects cancer processes (e.g. cancer development and progression, tumor evolution and/or response to therapy).
• Integration of information across temporal and spatial scales: State-of-the-art quantitative measurement technologies have facilitated collection of chemical, molecular, structural, interactome, and localization data within and across cell populations in the tumor microenvironment. Systems analyses and network reconstruction using single scale data (i.e. gene, mRNA, protein, metabolite, cell) do not necessarily predict behavior at another scale and translating information across space and time remains a challenge. Therefore, research projects addressing how information networks and mechanistic insights at one scale coordinate, integrate, and/or translate into tumor behaviors at lower or higher scales are warranted.
• Tumor behaviors reflecting single cell characteristics: Advanced quantitative single-cell measurement technologies at the genomic, epigenomic, transcriptomic and protein level of individual cells have provided significant insights into tumor heterogeneity and clonal evolution during tumor initiation, development, and adaptation in response to therapy. However, how single cells or single clones contribute to tumor biology is not well understood. Proposed research projects may attempt, for example, to explain how variations in single cell or single clone molecular characteristics or network dependencies contribute to immune system modulation or microenvironmental remodeling.
• Systems-level analyses of the role of the microbiome in cancer: How the human microbiota contributes to the pathogenesis of specific cancers likely reflects the interplay among the microbiome, other environmental exposures (i.e. diet, drugs, co-infection), and the underlying host genetic and/or phenotypic heterogeneity. Efforts are warranted towards mechanistic models of host-microbiome interaction in tumor initiation, progression, or treatment. For instance, Research Projects may incorporate microbe-associated peptides, ligands, or small molecules into cancer systems biology models that predict host cell survival, death or response to treatment. In addition to other mechanistic studies, systems models that address the adaptive capabilities of the microbiota to alter their host niche (e.g. microbe regulation of inflammasome signaling in intestinal epithelial cells) are encouraged.
• The combination of systems and synthetic biology for understanding disease mechanisms in cancer: Multivariate systems biology model predictions could be tested using synthetic biology approaches that engineer multiple controllable cellular components. Research Projects may focus on the development and/or employment of synthetic biology tools (such as engineered circuits, networks, cells) for the purposes of populating, training, or testing cancer systems biology models. Projects utilizing cancer systems biology approaches to inform synthetic biology tool design for the ultimate purpose of studying the mechanism of cancer-related processes are also encouraged. Studies should be completed in cancer-relevant experimental models, such as cancer cell lines, genetically engineered animal models, or patient-derived xenografts.
• Hierarchical models of cancer: In addition to integrating data across molecular, genetic, protein and cellular scales, systems biology approaches could be utilized to bridge and/or inform models at the organ, patient, and population level. Examples include using mechanistic systems biology predictions to inform pharmacokinetic models in patients or utilizing computational, mathematical or statistical formalisms to bridge a mechanistic systems biology model at one scale and a population-level model at the other. Applicants may propose projects to address technical challenges involved in linking models and data across these cancer-related hierarchical scales.
• Systems biology aided clinical trial design: Precision medicine requires integrating patient-specific characteristics with knowledge gained in pre-clinical studies, such as, but not limited to, differences in multicellular or multiclonal drug response, staggered temporal dosing schedules, and/or dynamic prediction of effective combination therapies. Research projects that utilize systems biology approaches and culminate in informing clinical trial designs (to be supported under another mechanism) are appropriate under this FOA. For example, projects might utilize cancer systems biology approaches to perform in silico clinical trials whose outcome determines optimal patient populations for clinical trials.

Resources Relevant to CSBC Research Projects

CSBC Research Project awardees will have the opportunity to take advantage of consortium-wide working groups and organizations, and will be expected to participate in consortium-related activities within the CSBC. For example, Research Project awardees may participate in and/or lead network pilot projects from the Pilot Project fund allocated to the CSBC/PS-ON Coordinating Center.

Depending on the focus of a given Research Project, interactions with investigators from other NCI-supported consortia may be appropriate. In particular, Research Projects focused on bridging molecular and population-level models may benefit from access to the resources within the NCI Cancer Intervention and Surveillance Modeling Network (CISNET).

Not Appropriate for This FOA

The following are examples of projects that are not appropriate for applications submitted to this FOA:

• Research projects focused on purely bioinformatic analyses of omics data that are not borne of a specific hypothesis.
• Research projects for which experimental validation or testing of systems biology predictions is not proposed.
• Research Projects proposing correlative studies related to host-microbiome interaction with no underlying mechanistic interrogation, or those cataloging changes in the microbiome due to tumorigenesis or drug treatment without a cancer systems biology model.
• Research Projects proposing to build cancer detection or treatment systems utilizing synthetic biology tools.
• Research Projects proposing validation of clinical correlative statistical models.

Applicants considering a larger scope of research than a single project may consider applying for a CSBC U54 Research Center (RFA-CA-15-014).

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

Higher Education Institutions

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

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

• 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)

Governments

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

Other

• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

Due to the multi-disciplinary nature of the projects and the focus on collaboration and expertise sharing, this FOA strongly encourages the use of the multi-PD/PI mechanism. The CSBC Research Project PD/PI (contact PD/PI for applications with multiple PDs/PIs) should be a scientist with expertise in cancer systems biology.

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

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

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

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

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Shannon Hughes, Ph.D.
Division of Cancer Biology (DCB)
National Cancer Institute (NCI)
Telephone: 240-276-6224
Email: [email protected]

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed. The following guidance also applies.

The CSBC Research Project PD/PI (contact PD/PI for applications with multiple PDs/PIs) should be a scientist with expertise in cancer systems biology. Primary expertise can be established through a body of work that demonstrates impact on the field. It is recognized that there may be instances where a single PD/PI will already have expertise in cancer systems biology and may not need to use the multi-PD/PI option, but applicants are otherwise encouraged to take advantage of the multi-PD/PI option.

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

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

Appropriate travel funds must be included in the proposed budget to support travel for at least one CSBC Research Project PD/PI to the Annual CSBC Investigators Meeting.

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

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

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

Specific Aims: State the specific aims of the Research Project and provide the rationale for the proposed systems biology approach. Within the Specific Aims, please state if the application addresses one of the topic areas highlighted in Part 2, Section I.

Research Strategy: Applicants should structure Research Strategy using the standard sub-sections Significance, Innovation, and Approach as defined in the standard SF424 instructions. Under these sub-sections, address the following specific aspects:

• Explain how the proposed Research Project uses systems biology and/or integrated systems biology/population science approaches for research goals that could not be accomplished utilizing molecular, cellular, biochemical, or computational/mathematical approaches alone.
• Highlight any innovative systems biology methodologies utilized or developed within the context of the proposed research.
• Explain how the Research Project will contribute to the goals of the Cancer Systems Biology Consortium.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan;
• Sharing plans are expected to address the NIH Genomic Data Sharing Policy if applicable, i.e., if the proposed studies will generate large-scale human or non-human genomic data (see NOT-OD-15-027 for additional guidance).
• Data, software, and models from this FOA are expected to be shared in accordance with the policies determined by the CSBC U24 Coordinating Center. For more information see the Cooperative Agreement Terms and Conditions of Award in Section VI of this FOA.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or 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: All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow our Post Submission Application Materials policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The emphasis and maximal priority of this FOA are on projects that address highly challenging cancer problems that can be solved only through systems biology approaches with the experimental testing and/or validation of computational predictions. To be viewed as meritorious, projects proposed must be strong in both aspects and must be based on appropriately integrated mutidisciplinary efforts.

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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: To what extent does the project pose a challenging cancer question that can only be answered through a systems biology (or the integrative population science and systems biology) approach?

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

Specific for this FOA: Does the team include the necessary multidisciplinary capabilities with both computational/mathematical modeling expertise as well as cancer biology experience/capabilities to accomplish their goals?

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: Are the proposed cancer systems biology approaches innovative?

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

Specific for this FOA: Is the approach based upon the combination of hypothesis-driven data collection (experimentation) and modeling/theoretical approaches indicative of cancer systems biology? Are the plans for validation or testing of systems biology (or integrative systems biology and population science) predictions well thought out and sufficient to accomplish the goals of the project?

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 children, justified in terms of the scientific goals and research strategy proposed?

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 for this FOA: What is the potential of the proposed project to meaningfully contribute to the goals of the CSBC and other NCI-related consortia (e.g. CISNET), as applicable?

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.

For research that involves human subjects but does not involve one of the six 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed 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 children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

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.

Not Applicable

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.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

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

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

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• Overseeing the scientific research in the Research Project, analyzing and interpreting research data, reporting results to the scientific community, and disseminating approaches, methods, models, software, and tools broadly.
• Agreeing to be an active participant in the CSBC, including attending the Annual Investigators Meeting, participating in other consortium sponsored meetings and workshops, and participating in collaborative activities.
• Promoting trans-CSBC and external collaborations to advance cancer systems biology research. Research Project awardees may participate in and/or lead network pilot projects from the Pilot Project fund allocated to the CSBC/PS-ON Coordinating Center.
• Participating in collaborative activities with other relevant NCI consortia as deemed appropriate by NCI program staff.
• Serving on the CSBC Steering Committee. The CSCB U01 Research Project PD(s)/PI(s) (contact PD/PI for applications with multiple PD(s)/PI(s)) are required to serve as members of the Steering Committee on a rotating basis (see Areas of Joint Responsibility below).
• Abiding by the governance of the CSBC and all program policies agreed upon by the CSBC Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations.
• Reporting progress to the NCI Program Officials on all CSBC Research Project research 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 program staff members on a semi-annual basis.
• Ensuring that data are deposited in a timely manner in appropriate publicly available locations, and that models, software, and other tools and resources developed as part of this Research Project are made publicly available according to CSBC policies. Additionally, all CSBC Research Projects awardees will be required to utilize the Resource Coordinating Hub, a resource to be developed by the CSBC/PS-ON Coordinating Center that will be funded under the companion FOA RFA-CA-15-015.
• Ensuring that results of the Research Project is published in a timely manner.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. Participating CSBC Research Center members are also encouraged to organize and participate in other Consortium meetings and workshops, organize collaborative activities, and promote Trans-Consortium 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:

One or more designated NCI Program staff members will have substantial involvement as Project Scientists in the awards under this FOA. The specific roles of the substantially involved NCI staff members include the following activities:

• Serving as voting members of the CSBC Steering Committee.
• Assisting the Steering Committee, the CSBC/PS-ON Coordinating Center, and individual U54 and U01 awardees in avoiding unwarranted duplications of effort across the CSBC.
• Facilitating collaborative research efforts that involve multiple CSBC research components and would be suitable for consideration by the Collaboration and Pilot Project Hub to be managed by the U24 Coordinating Center.
• Assisting the awardees as a resource in facilitating their broader interactions with other NCI and NIH programs to disseminate results, tools, and models from the CSBC and take advantage of existing NIH/NCI resources and infrastructures. This will specifically include acting as a liaison between the CSBC and PS-ON and between the CSBC and CISNET.
• Ensuring that the Resource Coordinating Hub, to be developed by CSBC/PS-ON Coordinating Center, is provided to CSBC and PS-ON members in a reasonable and expeditious way.
• Evaluating the effectiveness and facilitating consortium-wide adoption of Resource Coordinating Hub practices.
• Monitoring the operations of the CSBC awardees and making recommendations on overall project directions and allocations of CSBC Center funds.
• Reviewing the progress of the CSBC awardees (including CSBC/PS-ON Coordinating Center), conducting periodic site visits, and taking other actions as needed.
• Participating in organizing annual CSBC meetings, specialized workshops, and webinars of the consortium.
• 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:

The CSBC will have a Steering Committee as a governing body. The CSBC Steering Committee will consist of:

• The contact PD/PI (for CSBC Research Centers with multiple PD(s)/PI(s)) from each awarded CSBC Research Center.
• A maximum of six PD(s)/PI(s) (for U01 Projects with multiple PD(s)/PI(s)) from the awarded CSBC U01 Research Projects. Representatives from U01 Research Projects will be rotated every 18-24 months to allow all U01 contact PD(s)/PI(s) to serve on the Steering Committee. A PD/PI can vote only once if they have contact PD/PI status on two CSBC grants.
• NCI Project Scientist(s), maximum 2

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

Two PD(s)/PI(s), representing two different CSBC awards, will be selected to serve as chairs of the Steering Committee starting at the first meeting of the Steering Committee following award issuance. All CSBC 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 contact PD/PI of the awarded CSBC/PS-ON Coordinating Center (U24) will be a permanent non-voting member.

The CSBC Steering Committee will meet annually at the CSBC Annual Investigator Meeting and as needed.

The CSBC Steering Committee will:

• Identify scientific and policy issues that need to be, or can benefit by being, addressed at the Consortium level and develop recommendations to NIH/NCI Program Officials for addressing such issues.
• Review progress of the CSBC toward meeting the overall Consortium goals.
• Ensure that all CSBC members utilize the CSB Hub developed by the U24 CSBC/PS-ON Coordinating Center.
• Approve and prioritize the funding of the collaborative pilot projects administered by the U24 CSBC/PS-ON Coordinating Center utilizing the restricted Pilot Project Fund.
• Coordinate dissemination of Consortium output to the broader cancer research community.
• Review the potential of Shared Resource Core(s) at individual Research Centers to serve the needs of other Research Centers or Research Projects and develop appropriate policies for such activities.
• Ensure that the Consortium takes advantage of existing NCI and NIH resources and programs.
• Establish, as necessary, subcommittees to ensure progress of the individual Centers, Projects, and the Consortium.

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: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

A final progress report, 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. In addition to standard information, the annual report must include (under Section B "Accomplishments") a summary of the outcomes associated with each trans-Network pilot project in which the Research Project is involved

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

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Shannon Hughes, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6224
Email: [email protected]

For issues related primarily to the population science component of the Bridging the Gap Between Mechanistic Systems Biology and Population Science focus area, please direct inquires to:
Eric J. (Rocky) Feuer, Ph.D
National Cancer Institute (NCI)
Telephone: 240-276-6772
Email: [email protected]

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

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]

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.