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 investigator-initiated research efforts aimed at the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. Tissue-engineered in vitro and ex vivo systems that reflect the pathology and physiology of human disease are needed within the existing continuum of cancer models as new tools for studying cancer biology. Complementary implementation of these tools with existing cancer models is envisioned to ultimately lead to advances in cancer prevention, early detection of aggressive cancer, diagnosis and treatment. To date, only a handful of validated, biologically relevant tissue-engineered technologies exist for addressing specific cancer research questions. Recent technological advances in biomimetic tissue-engineered systems for the purposes of regenerative medicine could allow for new, innovative applications to cancer research. This FOA will support multidisciplinary research projects, and the funded investigators will collectively establish and participate in the Cancer Tissue Engineering Collaborative (TEC) Research Program. Projects will focus on the development and characterization of in vitro systems using tissue-engineered technologies that mimic tumor biology to elucidate specific cancer phenomena that are otherwise difficult to examine in vivo.

This FOA is intended to encourage collaborative, multidisciplinary projects that engage the fields of cancer research with regenerative medicine, tissue engineering, biomaterials, and bioengineering. It is also expected to catalyze the advancement of innovative, well characterized in vitro and ex vivo systems available for cancer research, expand the breadth of these systems to several cancer types, and promote the exploration of cancer phenomena with biomimetic tissue-engineered systems beyond commonly studied areas such as cell migration and angiogenesis. Applicants are encouraged to leverage existing resources, such as in vivo models, imaging techniques, or computational models.

Biomimetic Tissue-Engineered Technologies

Overview. Biomimetic tissue-engineered technologies combine information from the study of tissue structure and function with engineering, materials science, physics, chemistry, mathematics, and imaging to generate reproducible tissue in vitro that mimics three-dimensional (3D) in vivo tissue. When functionally characterized, the added control and reproducibility of tissue-engineered technologies can provide an enhanced understanding of cell and tissue biology under normal and pathological conditions. Tissue-engineered technologies have played a key role in advancing regenerative medicine over the past two decades, leading to the fabrication of systems that mimic components of several tissue types. New advances in biomaterials, engineering technologies, and stem cell engineering have greatly facilitated the engineering of tissues for in vitro applications, including studies of tissue morphogenesis, development, disease progression, molecular therapeutics, and drug toxicity screening in human tissues. As these technologies advance, opportunities exist for innovative ideas to leverage them in order to study other diseases including cancer and pre-malignant states.

Biological Relevance and Advantages. Biomimetic tissue-engineered technologies offer great precision and control of their physical and spatial parameters and components. These technologies bridge the discontinuity in cancer research models between two-dimensional (2D) and three-dimensional (3D) spheroid or cell-laden extracellular matrix in vitro systems and in vivo animal models. Limits exist in the types of biological questions that can be answered with 2D and 3D systems due to the inability to replicate tissue-specific pathophysiology. On the other hand, limitations of in vivo animal models include costly assays and the challenge of precisely controlling experimental variables of the tumor microenvironment, such as spatial, molecular, and physical information. To address these limitations of conventional in vitro systems and in vivo animal models, well-characterized tissue-engineered in vitro systems that incorporate tissue pathology and physiology are needed within the cancer model continuum.

Biomimetic tissue-engineered technologies provide a complex context to noninvasively study and visualize cancer biology in vitro, and deliver complimentary insights to what can be gleaned from more complex in vivo models. The validation of the biological relevance of these systems is vital for demonstrating reproducibility and precision that replicate tumor biology. Characterization of tissue-engineered technologies for validation of tumor biology could include the demonstration and visualization of complex tissue structure, pathology, and physiological function that recapitulate key aspects of tumor biology relevant to the specific hypothesis to be tested. Pertinent to reproducibility, it will also be important to characterize all cell sources demonstrating that they indeed represent the expected species, tissue and cell type from which they were derived. The biomimetic tissue-engineered technologies are not expected to fully recreate every component that would be observed in a tumor in vivo; rather they are expected to recapitulate the essential components that result in a tissue mimetic with accurate structure, pathology, and physiological function important for studying and answering well defined clinically relevant cancer research questions.

NCI Assessment. Three workshops have been sponsored by the NCI to assess the status of tissue-engineered systems in cancer and to identify gaps.

In April 2012, a broad-scope workshop was held to discuss areas where physical sciences principles from tissue engineering and developmental biology could open new avenues in cancer research. Participants highlighted the need for development of synthetic in vitro and ex vivo engineered systems to better probe key factors in tissues and their microenvironment important in cancer. The consensus of the participants was that these factors could be best studied in physiologically relevant and controlled tissue-engineered systems.

To further explore the status of tissue-engineered technologies in cancer, a second targeted workshop was held in February 2014. The workshop, entitled Biomimetic Tissue Engineered Systems for Advancing Cancer Research, highlighted examples of how tissue-engineered technologies are currently being applied to cancer research to study angiogenesis, migration, and therapeutic resistance. Workshop participants identified areas for future focus based on existing research and gaps in cancer biology.

Finally, in April 2015, a joint workshop was held with the National Science Foundation on 'Additive Manufacturing for Tumor Engineering'. The workshop highlighted several barriers to constructing tissue-engineered systems for cancer research, including the need for their robust pathophysiological characterization. Participants recommended the formation of multidisciplinary partnerships to construct and characterize tissue-engineered models of cancer. It was suggested that characterization of systems could include, but not be limited to, biological comparisons of in vivo and clinical datasets.

This FOA will support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. Critical to this FOA will be characterizing the biological relevance of the tissue-engineered technologies. Applicants will be expected to take a novel engineering approach to define the critical features and parameters for the proposed system, how they are sufficient to mimic the physiology and pathology of the specific cancer question under study, and what characterization will be needed to validate the biological relevance of the system. Characterization could include the demonstration of relevant tissue structure, tumor biology, pathology, and physiological function that replicates the aspect of tumor biology that will be studied using the proposed system. The long-term goal is that the technologies might begin to have novel applications addressing questions in cancer biology, prevention, early detection of aggressive cancer, diagnosis and therapy.

Possible research areas of emphasis include the development and characterization of tissue-engineered biomimetic technologies, such as the following:

• Engineered native and/or synthetic scaffolds (e.g., hydrogels, nanofibers, 3D printing, decellularized matrix), bioreactors, and microfluidic devices to better understand the role of the structure and spatial organization in cancer initiation, progression, and treatment. The biomimetic systems could incorporate functionalized biomaterials that mimic tumor properties and are designed to probe cellular behaviors such as crowding, coupled interactions and/or cooperativity, and autocrine/paracrine behaviors at the molecular and cellular length scales.
• Cellular, mechanical, and secreted chemical factors of the tumor microenvironment such as stromal cells, exosomes, immune components, gradients of cytokines, growth factors and hormones, oxygen tension, pH, and extracellular matrix structure.
• Perfusion, lymphatics, interstitial pressure, passive flow, or immobile and soluble gradients to study the role of tumor physiology and immune responses on cancer biology, diagnosis, and treatment. Molecular probes could be incorporated to obtain quantitative and dynamic functional measurements.
• Technologies to facilitate measurements of bi-directional signaling, stresses, and dynamics of complex tumor systems, such as responsive materials, molecular probes, or genome editing tools that can be regulated or monitored with minimal invasiveness. Integration of advanced imaging modalities could allow visualization of dynamic cell and tissue processes across space and time.
• Engineered tissues capable of long-term culture to examine cancer initiation and dormancy over several weeks.
• Coupling with computational models to understand the emergence of tumor form, function, and heterogeneity from genetic or spatial information.
• Multi-organ engineered culture systems to probe organ-to-organ interactions during cancer progression and treatment.
• Systems to model cancer progression from pre-neoplastic lesions to invasive and metastatic disease; to develop biomimetic systems amenable to imaging for early detection of aggressive cancer, diagnosis and prognosis; and to select preventive and therapeutic agents.

The above list of possible research areas is intended to be a set of examples and is not a comprehensive list.

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

Other

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

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

Specific to this FOA: This FOA strongly encourages the use of the multi-PD/PI option given the required multidisciplinary expertise for developing and characterizing state-of-the-art biomimetic tissue-engineered technologies for understanding cancer pathophysiology. At least one project team member must have prior experience and/or necessary qualifications in cancer research to support the successful execution and implementation of the proposed project.

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:

Nastaran Z. Kuhn, Ph.D.
Division of Cancer Biology (DCB)
National Cancer Institute (NCI)
Telephone: 240-276-7610
Fax: 240-276-7861
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.

All instructions in the SF424 (R&R) Application Guide must be followed. At least one project team member should have prior experience and/or necessary qualifications in cancer research.

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

Proposed budgets must also include appropriate travel funds to support travel for at least one PD/PI to an annual Cancer TEC Research Program meeting in the Washington, DC area.

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:

Research Strategy: The Research Strategy should clearly describe and consist of the following sub-sections:

State-of-the-art technology

• The tissue-engineered technology and whether it is an adaptation of an existing technology or a new technology. What the advantage is of the proposed technology/methodology over existing/alternative technologies.
• Additional novel concepts, approaches, tools, or technologies for the proposed studies.

Research Approach

• The cancer research problem to be investigated, its significance, and the relevance of the technological approach to the cancer research question being asked. How the proposed approach could ultimately bring novel insight to cancer biology and oncology.
• The research design, conceptual procedures, and analyses to be used to accomplish the Specific Aims of the project and the rationale for selecting these approaches.
• The potential difficulties and limitations of the proposed procedures and alternative approaches to achieve the aims.

Characterization

• How the technology will be characterized to demonstrate that it replicates the aspect of tumor biology that will be studied (e.g., the relevant tissue structure, tumor biology, pathology, and physiological function).
• How the use of the proposed cell types are sufficient to capture the complexity of the tissue(s) being studied and how the cell source(s) used in the project will be characterized to demonstrate that they indeed represent the expected species, tissue and cell type from which they are derived.
• A tentative sequence or timeline for the project.

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.

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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

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

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

Part I. 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 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 FOA, note the following:

The overarching goal of the Cancer TEC Research Program is to support the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. The long-term goal is that the technologies begin to be applied to address questions in cancer biology, prevention, and early detection of aggressive cancer, diagnosis and therapy.

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 for this FOA: If the aims of the project are achieved, how will technological advances in cancer model systems have been improved? Will the approach/methodology have an advantage over existing/alternate approaches? Does the research outcome have the potential to add new insights to the cancer research problem that is being addressed?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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: Do the project team members and/or associated collaborators engage the fields of cancer research with regenerative medicine, tissue engineering, biomaterials, or bioengineering where appropriate or needed? Does at least one project team member have prior experience and/or necessary qualifications in cancer research to support the successful execution and implementation of the proposed project?

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

Specific for this FOA: How innovative is the use of the proposed technology (whether existing or new) in the context of cancer research? Do similar tools currently exist for cancer research?

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: Does the applicant take a novel engineering approach to define the critical features and parameters for the proposed system and describe how it will be demonstrated that these features are sufficient to mimic the physiology and pathology of the specific cancer question under study? Is the proposed use of particular cell types sufficient to capture the complexity of the tissue(s) being studied, and are the cell sources characterized demonstrating that they indeed represent the expected species, tissue and cell type from which they are derived?

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: Has the applicant established collaborations engaging the fields of cancer research with regenerative medicine, tissue engineering, biomaterials, or bioengineering where they are appropriate or needed to facilitate achievement of the research goals? Does the project take advantage of various bioengineering tools, biomaterials, and cell resources available to the scientific community? Do the letters of collaboration and institutional support show strong commitment to the project?

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 National Cancer Institute 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 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.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 http://www.hhs.gov/ocr/civilrights/understanding/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 http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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:

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

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

• Oversee the project as a whole, including planning, directing and executing the proposed scientific activities, directing scientific/technical direction of the team, and disseminating approaches, methods, models, software, and tools broadly;
• Identify potential impediments to the execution of the research goals during the course of the award period, implement corrective action, and apprise the NCI Program Official;
• Cite the appropriate Cancer TEC research grant number on all related scientific research publications and acknowledge the appropriate NIH Institute(s)/Center(s) funding the grant;
• Travel at least one PD/PI to an annual Cancer TEC Research Program Meeting in the Washington, DC area;
• Coordinate Cancer TEC Research Program activities with the NCI Program Official. These actions may involve (but will not be limited to) the participation in appropriate coordinating meetings and/or working groups, and/or teleconferences as needed, participation with other related NCI or NIH programs, participating in Program meetings, workshops, and activities to be defined over the course of the award period;
• Collaborate with members of the Cancer TEC Research Program and external collaborators to advance and cross-test emerging biomimetic tissue-engineered technologies;
• Organize scientific working groups as needed to facilitate collaborative projects and cross-testing of experimental and theoretical concepts;
• 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 HHS, PHS, and NIH policies.

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

The designated NCI Program Official to be named in the award notice, acting as Project Scientist, will be substantially involved in this project above the normal stewardship in awards as described below.

Specific NCI Project Scientist responsibilities will be to:

• Monitor the progress of the U01 project, help coordinate research approaches, and contribute to the shaping of research projects or approaches as warranted. The NCI Project Scientist will support and facilitate this process but will not direct it;
• Serve on coordinating groups or working groups as appropriate for facilitating efforts that require coordinated action;
• Coordinate and facilitate interactions and collaborations among the Cancer TEC Research Program awardees;
• Participate in organizing Cancer TEC Research Program annual meetings and strategic workshops as needed;
• Facilitate interactions of Cancer TEC Research Program awardees with other NCI and NIH programs to effectively leverage existing NIH resources and infrastructures;
• Organize and conduct regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed; and
• Suggest reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met. Specifically, the NCI Project Scientist may have the option to recommend, within the NIH grants policy, the withholding or reduction of support, suspension, or termination of a cooperative agreement that substantially fails to comply with the Terms and Conditions of the award.

Areas of Joint Responsibility include:

The NCI Project Scientist(s) and the PDs/PIs of the Cancer TEC Research Program will be jointly responsible for the coordination of intra-program activities and the scientific integration of individual projects in the Program and when warranted with other appropriate NCI/NIH programs. Joint responsibilities include:

• Developing working groups and trans-project efforts as needed.
• Organizing and conducting regular meetings to share progress and foster collaborations between the awardees, either by teleconference, videoconference, or face-to-face, as needed.

Although the Cancer TEC Research Program will not have any separate formal governing body, these activities may involve the formation of a Coordinating Group. The primary role of the Coordinating Group will be to serve as an interface between the individual Cancer TEC Research Program U01 projects and when warranted other appropriate NCI/NIH programs. Such a Coordinating Group, if formed, will:

• Consist of the PD(s)/PI(s) and the NCI Project Scientist from each U01 project.
• Convene to assess scientific progress, identify new research opportunities, establish priorities, consider policy recommendations, propose publication guidelines and discuss strategies for integration of research efforts.
• Meet in person or by teleconference, with additional NCI/NIH staff, at least once per year.
• The NCI Project Scientist(s) will initiate the formation of the Coordinating Group and will facilitate its activities.

The NCI Project Scientist(s) may additionally form an External Scientific Panel (ESP) composed of senior non-federal scientists who are not directly involved in the activities of the Cancer TEC Research Program. The ESP would advise NCI on the progress of the Cancer TEC Research Program, on the contributions of individual projects and/or project collaborations, and on the progress and effectiveness of the Program as a whole.

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 academic members who are not involved in the study will be convened. 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.

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

For general inquiries about this FOA and for issues related primarily to basic cancer biology.
Nastaran Z. Kuhn, Ph.D.
Division of Cancer Biology (DCB)
National Cancer Institute (NCI)
Telephone: 240-276-7610
Email: [email protected]

For issues related primarily to cancer prevention or the early detection of aggressive cancer.
Richard Mazurchuk, Ph.D.
Division of Cancer Prevention (DCP)
National Cancer Institute (NCI)
Telephone: 240-276-7126
Email: [email protected]

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

Martinson Owusu
National Cancer Institute (NCI)
Telephone: 240-276-6297
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.