NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 enable the development of nanotechnology-based comprehensive solutions to significant problems in cancer biology and/or oncology and produce cancer care relevant applications with clinical utility. To address this goal, applications are solicited for Centers of Cancer Nanotechnology Excellence (CCNE). CCNEs will provide the main research infrastructure for the NCI Alliance for Nanotechnology in Cancer program. Within the Alliance, CCNEs will serve as a network assembled to develop research and translational capabilities, and as individual programs enabling effective multi-disciplinary team research to advance nanotechnology-based cancer prevention, detection, diagnosis, and/or treatment. To build multidisciplinary teams needed for the goals of this FOA, each proposed CCNE must provide leadership in medicine/biological sciences, as well as in the fields of chemistry, physics, or engineering. In addition to strong, integrated research programs, these centers will also provide shared research support and other resources across the Alliance and to the broader research community. It is expected that, as a part of the Alliance, CCNEs will ultimately generate novel nanotechnology-based preventive, diagnostic, and therapeutic approaches to modulate and overcome cancer processes in ways that are currently not available and cannot be accomplished using existing state-of-the-art technologies.

This FOA will support a network of CCNEs pursuing research and development of techniques and tools based on nanotechnology that are capable of producing clinically relevant cancer care applications. It is expected that each Center during the award period will complete pre-clinical stages of development of these nanotechnology-based cancer care solutions as a result of the CCNE award. Although clinical trials are beyond the scope of this FOA, all CCNEs must be strongly committed to and capable of further translation of the technologies/tools under development. Therefore, specific research projects and efforts proposed by all CCNE applicants must be oriented towards generating outcomes that will pave the way to clinical trials. CCNE applicants are strongly encouraged to proactively seek other sources of funding that would allow for clinical trials to commence, even as early as during the award period.

Nanotechnology in the context of this FOA. To be responsive to this FOA, the proposed nanotechnology approaches, materials, devices, and technologies should be clearly distinguishable from their classical counterparts and must meet the following criteria:

• Functional components of devices or base materials either fabricated, assembled, or synthesized, must be at dimensions of 300 nm or less;
• Materials used and/or proposed to be developed must be either synthetic or biologically-based materials that are engineered to provide novel properties or modified functions due to their controlled assembly or synthesis at the nanoscale.

Non-responsive criteria. This FOA will NOT support projects that:

• Propose only the use of naturally-occurring materials (e.g., polysaccharides, proteins, viruses) that are not specifically engineered or modified for the intended function;
• Propose the use of nanotechnology-based devices for DNA sequencing;
• Involve clinical trials or in vivo studies in human subjects;
• Focus on nanotechnology solutions for AIDS/HIV even in the context of cancer.

Applications including such projects will be viewed as non-responsive. Non-responsive applications will not be reviewed. In vitro investigations that employ clinical biospecimens or the theoretical modeling of human systems are within the scope of activities and will be considered for support by this initiative.

Potential of nanotechnology in oncology. Nanotechnology has the potential to overcome various existing barriers in cancer research and care and offer previously unattainable benefits to cancer care. Nanotechnology can lead to a generation of new diagnostic and therapeutic approaches with the potential to improve cancer care outcomes. Nanotechnology may also drive advances in other aspects of clinical oncology and cancer research. These potential benefits are being explored by the NCI through support of multi-disciplinary research under the umbrella of the NCI Alliance for Nanotechnology in Cancer (http://nano.cancer.gov, also referred to in this FOA as the "Alliance"). The Alliance was founded in 2004 and is committed to developing and applying nanotechnology to new cancer care applications.

NCI intends to continue support for research in three broad areas of nanotechnology-based cancer care applications: (1) early diagnosis using in vitro assays and devices or in vivo imaging techniques; (2) multifunctional nano-therapeutics, including nanoparticle-driven immunotherapies; and (3) devices and techniques for cancer prevention and control. Specific research directions, priorities, and needs for the reissuance of the Alliance program were identified by seeking feedback from the scientific community, which included:

• a Strategic Workshop on Cancer Nanotechnology held in June 2013 (the workshop's report can be found at http://www.ncbi.nlm.nih.gov/pubmed/24413533);
• an interactive website (https://nanocancer.ideascale.com); and
• a Request for Information (NOT-CA-13-017).

The participants of the Strategic Workshop clinical oncologists, cancer researchers, and technologists expect that further progress in the field will move along two parallel tracks: (1) on-going translation of maturing technologies to the clinical environment and (2) the development of new tools and techniques in the research arena. The community expects that, in the future, nanotechnology will become a core component of research and translational programs at all leading cancer research institutions and a significant part of comprehensive cancer care.

How to facilitate nanotechnology development and implementation? The potential for transformative impact warrants continued support for research programs employing nanotechnology for the prevention, detection, and treatment of cancer. There are, however, various barriers that need to be overcome to ensure efficient translation of laboratory discoveries to clinical trials and, ultimately, to clinical practice. Following the aforementioned consultations with the scientific community, the NCI identified the following significant and specific needs to be addressed:

• The need for cross-disciplinary collaborations and infrastructure to enable the integration of the biology and oncology knowledge base with physical sciences and engineering approaches to properly address relevant aspects of cancer;
• The need for goal-oriented, milestone driven developmental research programs in medical technologies to overcome the widening gap between discovery and early commercial development of diagnostics and therapeutics;
• The need for partnerships of academic researchers with industry to facilitate technology translation and commercialization;
• The need to establish efficient mechanisms for the pre-clinical development of nanotechnology-based platforms for cancer prevention, diagnosis, and therapy, including securing appropriate regulatory prerequisites for clinical trials [such as Investigational New Drug (IND) or Investigational Device Exemption (IDE) status granted by the Food and Drug Administration (FDA)];
• The need for standards and publicly available datasets of nanoscale materials and devices that would be fully characterized (e.g., their detailed physical, chemical, and physiochemical properties) and the need for a consolidated strategy for performing such characterizations in an integrated manner;
• The need for more information and data sharing on the characteristics and properties of nanomaterials through the use of public domain, non-proprietary databases; and
• The need for comprehensive nanotechnology training programs in multi-disciplinary environments focused on applying the tools of nanotechnology to critical problems in cancer research and clinical oncology.

The continued Alliance program will consist of the following mechanisms:

• Centers of Cancer Nanotechnology Excellence (CCNEs, covered by this FOA). CCNE teams will be required to pursue vigorous development of technologies that have practical clinical applications, up to and including the pre-clinical stage. These efforts should be integrated with research of a discovery nature and should contribute to the understanding of clinically relevant cancer problems.
• Innovative Research in Cancer Nanotechnology (IRCN) Awards. To complement the comprehensive approaches at CCNEs, IRCN awards (U01 funding mechanism, separate FOA PAR-14-285) will support smaller, well-defined projects aimed mainly at discovery research. Their focus will be on developing further understanding of nanomaterial interactions with biological systems and mechanisms of their in vivo delivery.
• Interdisciplinary Nanotechnology Training and Career Development. To enhance multidisciplinary training, T32 training programs dedicated to cancer nanotechnology will be supported through the Parent T32 Announcement PA-14-015. As defined in NOT-CA-14-035, the NCI will participate in this NRSA T32 program to further accelerate and intensify the development of a workforce highly skilled in nanotechnology research with medical applications.

The main objectives and expectations for each CCNE and the entire CCNE initiative include the following aspects:

• Research advances in applying nanotechnology to cancer research and care (primary emphasis): Significant advances are expected in the overall capacity to employ nanotechnology to understand, prevent, detect, and treat neoplastic diseases. Each proposed CCNE must be focused on an overarching problem or unmet need in cancer biology and/or oncology that may be addressed using nanotechnology approaches.
• Multi-disciplinary, collaborative approach to nanotechnology research and development: CCNEs are expected to facilitate broad multi-disciplinary research approaches and the development of productive collaborative relationships in their research programs (within each CCNE, as well as among all CCNEs and other Alliance awardees). To maximize the likelihood of generating a clinical trial-ready product/tool/technology and to facilitate its rapid commercialization, all proposed CCNEs are also expected to establish meaningful collaborations with for-profit organizations from the beginning.
• Increasing a cadre of competent cancer nanotechnology scientists: CCNEs are expected to provide efficient research, training, and career development opportunities for researchers of all levels of experience.

Center Theme. Each CCNE is expected to focus on a 'scientific theme' associated with a nanotechnology-based solution(s) to an overarching problem(s) in cancer biology and/or oncology. CCNE projects and overall Center organization are expected to support this overall 'theme'. The proposed nanotechnology solution(s) must be clinically relevant. This relevance (and a technology prospective application) may be in the area of cancer prevention, and/or diagnosis, and/or treatment.

The collective research and development efforts of CCNEs should strive for clinical utility, but at the same time should produce a significant body of knowledge contributing to the understanding of mechanisms behind improvements associated with the use of nanotechnology. This fundamental understanding will ultimately contribute to more informed and successful clinical translation.

Multidisciplinary Capabilities and Leadership. CCNE teams must have strong expertise in both applied nanotechnology and oncological research, including clinical translational activities. For both main areas, the expertise must extend to senior leadership levels. Each proposed CCNE research team should also have sufficiently deep expertise in other disciplines, as appropriate for their proposed research (e.g., in the fields of chemistry, physics, engineering, pharmacology, clinical sciences).

Coordination of Multidisciplinary Efforts. Given the need for integration of multidisciplinary efforts in each CCNE center, the scientific leadership and other senior members of the team are expected to have considerable experience in collaborative, multidisciplinary research and development relevant to the goals of the CCNE. Each CCNE must organize an Administrative Core to facilitate effort coordination and support the operation of the Center.

Research Projects. A set of three to five individual Research Projects are required for each CCNE. These projects should be synergistic to represent an integrated research program and support the proposed solution to the overarching cancer biology and/or oncology problem selected as the theme for the CCNE. Although the proposed research program collectively should lead to a prospective clinical application(s), an individual project may be either of a translational or basic research/discovery-oriented nature (as long as it is relevant to the overall theme and goals of the CCNE). Research Projects may be supported by optional Shared Resources Cores.

Developmental Program. Each proposed CCNE must have a program for the development of additional small projects that could broaden the CCNEs capabilities, serve as a career development vehicle for junior investigators, and/or address emerging needs and opportunities (for details see Section IV.2. Content and Form of Application Submission).

Possible Research Directions. The examples of appropriate research directions are listed below. These examples are not meant to be comprehensive. Additional topics/directions are also encouraged, providing they are consistent with the general requirements stated above. Moreover, the listed examples are NOT mutually exclusive and are NOT meant to confine the scope of a project. Various directions may be combined into a single project, if appropriate. For further details, see Section IV.2. Content and Form of Application Submission.

Examples of Translational Directions:

• Reformulation of candidate chemotherapeutics using nanotechnology;
• Nanotechnology-enabled multiplex diagnostic devices;
• Nucleic acid-based nanotherapies;
• Therapies that leverage changes in the physical properties of nanomaterials;
• Multi-modal nanoparticle imaging constructs;
• Instrumentation with nanomaterial components designed for cancer diagnosis or treatment;
• Engineered nanoparticles for effective immunotherapies;
• Combination therapies involving several drugs or different treatment modalities (at least one component should be nanotechnology-based);
• Nanotechnology-based techniques to monitor and enable surgery in real-time.

Examples of Basic Research/Discovery Directions:

• Development of next generation nanoparticles/nanosystems (e.g., bioactivatable/bioresponsive nanomaterials, nanomaterials with triggered release);
• Development of nanoparticles that exploit clinically favorable routes of administration (e.g., oral, nasal);
• Understanding of mechanisms of nanoparticle delivery to cancer cells and tissues in vivo (e.g., nanoparticle endosomal escape, Enhanced Permeability and Retention (EPR) effect);
• Novel approaches to nanotherapeutics design (e.g., strategies that utilize combinatorial library and screening approaches to optimize pharmacological/therapeutic effects);
• Methods to quantitatively assess in vivo properties (e.g., toxicity, pharmacokinetics, metabolism, biodistribution, biological interactions) of nanoparticle/nanomaterial;
• Integration of nanoparticle modeling and simulation approaches to guide rational nanomaterial design;
• Methods for physical characterization of nanomaterials and development of guidelines for nanomaterial validation and reproducibility standards;
• Identification and/or development of new tissue and animal model systems for the screening of nanotechnology compounds.

Tumor Types. All CCNE applicants are expected to concentrate their proposed efforts on one or a few rationally selected tumor types. For this FOA, a "tumor type" refers to either tumors of a specific tissue of origin or tumors with critical abnormalities in a particular molecular pathway(s) shared in cancers arising from a variety of tissues.

The Alliance, including CCNEs, will be governed by the Alliance Coordination and Governance Committee (CGC). The CGC will oversee and coordinate the activities of all CCNEs, IRCN awardees, and training programs. Details on the composition and functions of CGC are provided in Section VI. Award Administration Information, Terms and Conditions of Cooperative Agreement, Areas of Joint Responsibility .

As the efficiency of the funded research is an increasing priority for NCI, CCNEs will be required to participate in an external evaluation process of the Alliance initiative coordinated by NCI Program Staff. Outcomes to be assessed will include: impact of developed nanotechnologies on patient care, peer-reviewed publications, patent disclosures and filings, educational and community outreach programs, leveraged research funding, technologies brought to clinical trials, technology commercialization, and effectiveness of collaborative research development model. The purpose of the evaluation process is to monitor and assess the performance of the CCNEs in achieving the goals of this FOA. Criteria for the evaluation component will be developed by NCI Program Staff in partnership with the Alliance Coordination and Governance Committee (CGC) and other advisory committees of the program (as described in Section VI).

The applicants are encouraged to consider using, as appropriate, various relevant NCI-supported resources described below.

• Nanomaterials characterization. The NCI recognizes that further development of nanotechnologies for oncology purposes will benefit greatly from a concerted and coordinated effort to characterize the wide range of nanoscale materials and devices. The collection of this information will chart the common baseline and scientific data that would inform the research and development (R&D) community and define clinical and commercial pathways for integration of nanoscale diagnostics, imaging agents, and therapeutics. The NCI s Nanotechnology Characterization Laboratory (NCL; http://ncl.cancer.gov/) will provide infrastructure support towards the uniform and consolidated characterization of these materials and devices and thus will aid the translation of nanotechnology-derived cancer therapeutics and diagnostics from the advanced discovery-phase to clinical environment.
• Nanotechnology-related informatics. The NCI Center for Biomedical Informatics and Information Technology (http://cbiit.nci.nih.gov/) sponsors the cancer Nanotechnology Laboratory data portal (caNanoLab; https://cananolab.nci.nih.gov/caNanoLab/) and the National Cancer Informatics Program (NCIP) Nanotechnology Working Group (https://wiki.nci.nih.gov/display/ICR/Nanotechnology+Working+Group). caNanoLab is designed to enable sharing of nanomaterials data and to expedite and validate the use of nanoparticles in biomedicine. It provides support for the annotation and secure sharing of cancer-relevant nanomaterials with characterizations resulting from physico-chemical, in vitro, and in vivo assays. The NCIP Nanotechnology Working Group was established for researchers with a specific interest in informatics and computational approaches to nanotechnology. In addition to these efforts, NCI supports the Nanomaterial Registry (https://www.nanomaterialregistry.org/), which archives research data on nanomaterials and their biological and environmental implications from a broad collection of publically available nanomaterial resources.
• Animal models. NCI supports a broad spectrum of animal facility experimental resources (Laboratory Animal Science Program [LASP]: http://ncifrederick.cancer.gov/rtp/lasp/intra/lasp.asp and operates the Center for Advanced Preclinical Research [CAPR]: http://frederick.cancer.gov/Partnerships/Capr.aspx) that can conduct independent preclinical assessment of nanomaterials in vivo in a variety of predictive xenograft and genetically engineered mouse models, as well as syngeneic genetically engineered mouse-derived allografts.
• Other NCI research resources. CCNE applicants are encouraged to consider establishing partnerships with other groups, and divisions and programs within NCI that may benefit the CCNE's goals. For example, the awardees should take advantage of appropriate opportunities to work with The Cancer Genome Atlas (TCGA; http://cancergenome.nih.gov/), Cancer Target Discovery and Development (CTD2; http://ocg.cancer.gov/programs/ctd2) Network, Early Detection Research Network (EDRN; http://edrn.nci.nih.gov/), Clinical Proteomic Tumor Analysis Consortium (CPTAC; http://proteomics.cancer.gov/programs/cptacnetwork), and the Cancer Diagnosis Program (CDP; http://www.cancerdiagnosis.nci.nih.gov/).
• NCI translational resources. If appropriate, CCNEs may take advantage of NCI translational resources such as the NCI Experimental Therapeutics (NExT; http://next.cancer.gov/) program, and the services of the NCI’s Nanotechnology Characterization Laboratory (NCL; http://ncl.cancer.gov/). In addition, early CCNE interactions are encouraged with resources that may facilitate the ultimate translation of CCNE findings into the clinic, such as the NCI Clinical Translation Evaluation Program (CTEP; http://ctep.cancer.gov/), clinical trial programs, and Translation of Nanotechnology in Cancer (TONIC; http://nano.cancer.gov/collaborate/collaborating/nanotechnology.asp) consortium.

Beyond the Alliance and other NCI resources, CCNE applicants are also encouraged to take advantage of the range of additional existing opportunities in nanotechnology research and development through partnerships with other Federal agencies, such as the National Science Foundation (NSF); http://www.nsf.gov and the Department of Energy (DOE);http://science.energy.gov/bes/research/national-nanotechnology. The NSF and DOE programs are components of the National Nanotechnology Initiative (http://www.nano.gov/), a multi-agency framework of nanotechnology research that may serve as a resource for applicants to this FOA.

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
• U.S. Territory or Possession

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

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

Applicant Organizations

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

• 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.

Multiple PDs/PIs are required for this FOA. Applicants should identify at least one senior investigator (PD/PI) to lead clinical translational oncology and another senior investigator (PD/PI) to lead the applied nanotechnology.

PDs/PIs submitting a U01 application in response to the IRCN FOA PAR-14-285 or T32 application (through Parent T32 FOA PA-14-015) for the first due dates in October and September 2014, respectively, are NOT eligible to apply for the U54 CCNE award under this FOA as PDs/PIs. However, these individuals can serve as Project leaders, Core directors, or other key personnel within a U54 CCNE application.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. If more than one application is received from an individual applicant organization, each application must also be proposed by a separate team of investigators (i.e., with different PDs/PIs and other key personnel).

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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 and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

Dr. Piotr Grodzinski
Center for Strategic Scientific Initiatives
Office of the Director
National Cancer Institute
31 Center Drive, Room 10A52, MSC 2580
Bethesda, MD 20892-2580
Telephone: 301-451-8983
Fax: 301-496-7807
Email: grodzinp@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core	6 pages
Project (use for Research Projects)	12 pages per project
Core (use for Shared Resources Cores)	6 pages per core
Developmental (use for Developmental Program)	6 pages

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

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

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Research Projects: at least three projects required and no more than five allowed
• Shared Resources Cores: optional; no more than two allowed
• Developmental Program: required

When preparing your application in ASSIST, use Component Type Overall .

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

SF424 (R&R) Cover (Overall)

Complete entire form as instructed, with the following additional instructions: Title of entire CCNE application should reflect the overarching research and translational theme of the Center.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions with the following modifications:

Facilities & Other Resources

Document the available resources nanomaterial characterization and testing in animal models. Specifically, include a section named " Nanomaterial Characterization and Animal Resources". In the section, describe such aspects as nanomaterials characterization facilities and the access to animal studies and toxicology evaluation resources. Also describe ability to take advantage of the capabilities of NCI’s Nanotechnology Characterization Laboratory (NCL) (http://ncl.cancer.gov/).:.

Other Attachments:

Include attachment named "Previously Developed/Used Nanotechnologies". In the attachment, provide a summary documentation for all the members of the Center team (preferably in tabular format) to document:

a) the previously developed nanotechnologies relevant to cancer research and oncology;

b) any non-cancer related innovative nanotechnologies previously developed that may be relevant to the proposed Center theme; and

c) nanotechnologies (may be developed by others) that the members of the team used in cancer research and/or oncology.

Note: This attachment should be formatted as a cumulative summary of technologies for the entire team arranged by aspects a-c listed above. Indicate the institution of technology originators or users as appropriate (e.g., by a column in a table) but accomplishments listed in the individual biosketches should not be repeated.

Project/Performance Site Location(s) (Overall)

Enter primary site only.

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

Research & Related Senior/Key Person Profile (Overall)

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

Identify the two required PDs/Ps who will lead clinical translational oncology and the applied nanotechnology. (Additional PDs/PIs may be designated but are not required).

Biographical Sketch:

List in sub-section D (Research Support) of biosketches for all key personnel any relevant experiences in operating large research centers, program projects or other large-scale research endeavors.

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

Budget (Overall)

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

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

PHS 398 Research Plan (Overall)

Specific Aims: Describe the overall objectives for the proposed CCNE and Center Integration that will enable the development of a nanotechnology-based solution(s) to the significant cancer biology and/or oncology problem(s) to be addressed.

Research Strategy: The Research Strategy for the Overall component must consist of sub-sections A-C outlined below.

A. Overview of the Proposed CCNE Research Focus and Program. The proposed CCNE is expected to demonstrate a high level of scientific competence and strong capability for innovation and translation. Present the overall vision for the CCNE, including descriptions of the following:

• Scientific 'theme' of the Center describe the overarching cancer biology and/or oncology problem(s) and the proposed nanotechnology-based solution(s) to this problem(s). Demonstrate why nanotechnology is expected to provide a significant advantage as compared to other possible approaches.
• Proposed research program describe potential of the proposed research program under the Center Theme to change the landscape of cancer care applications. Explain the general rationale behind proposed Projects and Cores, and how these aspects of the program, including the balance between translational and discovery-oriented projects, will support the development of a nanotechnology-based cancer care application(s) with clinical applicability.
• In the above descriptions, include: (1) rationale behind selection of particular tumor types and/or pathways and animal models, and (2) why nanotechnology is capable of successfully addressing the prevention, diagnosis, and/or treatment needs of the selected tumor types.

B. Leadership and Center Organization.

• Describe organization of the leadership structure and overall Center structure (provide respective organizational diagrams).
• Outline the major strengths and relevant expertise of research team members and specific senior investigators in the context of the proposed Center Theme (not duplicating information already provided in the Biographical Sketch), and the advantages of their respective research fields and environments (e.g., academic or research centers of engineering, physical sciences, mathematics, chemistry, physics, computational and/or materials science).
• Outline how each of these investigators' groups will be directly involved with and actively contribute to the Center projects (such a relationship is required for each proposed project, but does not need to be unique for each).
• Center integration Describe the scientific and organizational integration of the different Center components. Explain how the proposed Research Projects and Cores are synergistic to one another, and why a Center mechanism is essential to accomplishing the CCNE's goals.

C. Capabilities and Experience. Each CCNE should be composed of investigators with a demonstrated capacity for collaboration and a strong record of innovation and translational capabilities.

• Outline how the CCNE leadership intends to capitalize on their collective experience in operating large-scale research programs.
• Describe research team's prior experience of working and publishing together, and other examples of significant collaborations.
• Describe capabilities (within and beyond the scope of the CCNE award) that are relevant to clinical translation and commercialization of technologies under development.
• Document the capacity of the proposed CCNE to advance technologies to be developed towards clinical translation and ultimate commercialization. Outline the role and level of commitment of a for-profit entity(ies) to be associated with the proposed CCNE.
• Indicate the effort distribution across all the participating institutions.

As part of delineating the scientific responsibilities of the multiple PDs/PIs, the lead roles in clinical translational oncology and applied technology should be identified.

Letters of Support: Provide letters of support for any collaborative agreements or subcontracts, including letters of support from for-profit entity (-ies) describing intent to form collaborations and specifying the commitments to the Center. All letters of support must be signed by senior institutional officials and must detail the institutional and leadership commitment from the participating institutions. Letters of support for the entire Center should be included in the Overall component. For-profit entities providing support to an individual Research Project should include a letter focused on global commitment to commercialization in the Overall component. Do not include here other letters of support for individual Research Projects or Cores.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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, are expected to address a Data Sharing Plan.
• This plan is expected to address data sharing for the complete application, but should only be included in the Overall component.
• The Data Sharing Plan should also address the sharing of nanomaterial data through appropriate publically accessible databases, as described in the "Cooperative Agreement Terms and Conditions of Award," Section VI.

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 preparing your application in ASSIST, use Component Type Admin Core.

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project (should be "Administrative Core")
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Director and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Administrative Core Director is expected to be a scientifically and administratively qualified senior researcher.
• In addition to the Core Director, the Administrative Core is expected to name a qualified Administrative Core Coordinator to direct the day-to-day operations of the Center, including responsibility for (under guidance of Core Director) the administrative, budgetary, and operational aspects of the Center.

Budget (Administrative Core)

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

Administrative Core Coordinator. Due to the complexity of the CCNE, the Administrative Core Director is strongly encouraged to propose and budget for an Administrative Core Coordinator to direct daily operations.

Site Visits and Annual Alliance Meetings. The Administrative Core will be responsible for planning and budgeting for annual site visits. Applicants must plan appropriate travel funds for the PD/PI, team leaders, and selected students to participate in the annual Alliance meetings. Budgets should account for the traveling of collaborators and other necessary costs.

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

PHS 398 Research Plan (Administrative Core)

Specific Aims: Describe objectives and goals for the Administrative Core. The Administrative Core should ensure the development of appropriate infrastructure to support research, training, and outreach in the Center, planning and evaluation activities, and facilitate Center integration as well as interactions outside of the Center.

Research Strategy: Describe how the Administrative Core will support and coordinate administration of the Center. Include descriptions of the following:

• Center Executive Committee. Each CCNE must form a Center Executive Committee that will be responsible for oversight of the Center's scientific direction, coordination and execution of project plans, and the review of milestones. Outline plans for the selection of the Center Executive Committee and plans for participation in committee activities, including plans for meetings and teleconferences. The Center Executive Committee should be composed of Center members.
• External Advisory Panel. Each CCNE must also recruit external experts who will serve as scientific advisors to the CCNE leadership. External advisory panel members should be selected from outside of the Center and should encompass the expertise needed to provide appropriate guidance to the Center. Describe the general composition of the external advisory panel(s) and how it will contribute to the Center's activities, but do not name specific individuals in the application.
• Pilot and Auxiliary Projects. Describe plans for the selection of Center Pilot and Auxiliary Projects by the appropriate committee or panel.
• Communication Plan and Data Management. Describe plans for maintenance of ongoing communication within and outside of the Center, especially when multiple performance sites are planned. This includes interaction with technology transfer groups at the home institution. Outline plans for data management and sharing, including plans for submission of nanomaterial information to caNanoLab, consistent with achieving the goals of the program. Outline the coordination of efforts to share data across the Center and the Alliance. These plans should include how, when, and what type of obtained data (raw, processed, and/or analyzed) will be shared with other Centers and Alliance investigators. In addition, all CCNE investigators are strongly urged to work together to ensure that all relevant data are deposited to appropriate public databases (no later than upon publication of findings in scientific journals). Note that at least one scientifically qualified individual is expected to be designated the nanomaterial data coordinator for the Center, but is not required to be named or selected until an award has been made.
• Training and Outreach Activities. Outline plans for training and outreach activities including creation/expansion of internal seminar series, mechanisms for scientific exchanges of researchers at various career levels across participating CCNEs (i.e., visits of researchers from your CCNE in other Centers and vice versa) and plans to disseminate information about the CCNE's capabilities and results to the broader clinical, cancer biology, and physical sciences communities (e.g., external seminar series, workshops, and working with patient advocates). CCNEs are encouraged to name a 'resident' patient advocate to support outreach activities, if appropriate.
• Annual Meeting. Outline plans for the travel of PDs/PIs and research team leaders and personnel to annual Alliance PD/PI meetings.
• Center Evaluation. Outline plans for the coordination of progress reports, site visits, and providing additional information to the NCI as need.

Note: All CCNE awardees will be expected to apply proper project management methods for planning, monitoring, and managing the workload over the award period and will be expected to share specific details of these aspects with NCI Program Staff members upon request.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.
• This item should not be completed here, but must be completed in the Overall component.

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.

Planned Enrollment Report (Administrative Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (Administrative Core)

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

When preparing your application in ASSIST, use Component Type Project.

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

Each CCNE is required to include three to five Research Projects closely pertinent to the research objectives (outlined in Section I of the FOA) and in combined support of the overarching problem in cancer biology and/or oncology selected as the theme for the Center. It is required that: (i) at least two projects are clinically-relevant translational projects with the ultimate goal of technology commercialization and (ii) at least one project is oriented mainly to basic research/discovery.

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Start each title with "Project 1:", "Project 2:", etc.
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.If appropriate, applicants may designate junior faculty investigators to lead or co-lead a project as a part of their career development activities.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Project)

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

The sum of the direct costs of all Research Projects should constitute at least 70% of the entire direct costs of the proposed Center's budget.

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

PHS 398 Research Plan (Research Project)

Specific Aims: Indicate whether a given project is a translational or basic/discovery project. Describe specific goals of the project and major milestones. Include the rationale and description of how the project fits into the overarching framework and goals of the Center.

Research Strategy: For each proposed project, the Research Strategy must consist of the standard sub-sections: Significance, Innovation, and Approach; and an additional "Milestones" sub-section (described below).

For the project concept, design, and approach, the additional requirements and guidance provided below must be followed.

General Requirements and Guidance Applicable to All Projects

• Well Developed, Rigorous Projects. Proposed projects are expected to be well developed conceptually and, in general, well supported by appropriate preliminary data from investigators laboratories, similar to typical R01 investigator-initiated projects. However, it is realized that original research data may be incomplete for some aspects of highly innovative nanotechnology projects, especially in areas that are at an earlier stage of development (e.g., nanotechnology-based immunotherapies, nanosystems that exploit alternative delivery routes). Projects with gaps in preliminary data may still be appropriate, provided they are conceptually highly innovative and rigorously integrate to the extent possible the available incomplete information for a given area from various sources.
• Transformative Potential. In the Significance sub-section, outline the potential impact on the field of the concept/hypothesis to be explored and/or nanotechnology solution to be developed. Considering advances in the cancer nanotechnology field, all projects proposed in the CCNE application are expected to have high potential for transformative outcomes. For example, they should go well beyond simple proof of concept demonstration of new clinically relevant features accomplished through nanoparticle-based therapeutic delivery or use of a nanotechnology-based diagnostic device. Projects expected to result in only incremental improvements over current solutions (based on either nano- or non-nanotechnology) are not likely to be viewed favorably by reviewers.
• Integration. At the end of Significance sub-section, include a brief paragraph (with the heading Integration ) to highlight how this project will contribute to the Center Theme and how it will benefit from a center environment.
• Proposed nanotechnology solution versus other options. In the Innovation sub-section, provide comparison of the proposed nanotechnology approach to available or possible classical approaches/options and/or currently used nanotechnology solutions. Discuss how the problem is approached at present and the limitations of current solutions, and how nanotechnology is expected to overcome these limitations. Summarize the key advantages and innovative aspects of the proposed technology, solution, etc. over other options. Generally, this comparison should be based on actual data (either investigators own preliminary data or literature data). In justified situations, however, theoretical considerations may also be used. Innovation of the proposed projects will be an important factor in their merit evaluation.
• Selection of Tumor Types. Generally, it is expected that all proposed projects within a Center will address the Center Theme by studies using collectively a few rationally selected tumor types (in terms of specific tissues of origin and/or critical abnormalities in particular molecular pathways shared in cancers arising from a variety of tissues). However, an individual project may focus, as appropriate and justified, on one or more different tumor types or types of abnormalities. In selecting specific tumor types, CCNE applicants are strongly encouraged to take advantage of the available resources with catalogs of clinical tumors that have been comprehensively characterized at the molecular genetics level (e.g., by programs such as The Cancer Genome Atlas (TCGA), http://cancergenome.nih.gov/, Therapeutically Applicable Research to Generate Effective Treatments (TARGET), http://ocg.cancer.gov/programs/target, and Cancer Genome Characterization Initiative (CGCI), http://ocg.cancer.gov/programs/cgci).
• Selection of Animal Tumor Models. Describe the animal tumor models you plan to use in your studies. To drive data comparability, the Alliance Coordination and Governance Committee (CGC) will suggest well-characterized and reproducible animal models, and experimental design, to be used for particular cancer types based on best practice guidelines and the input of investigators from all awarded CCNEs.

Milestones

For each project, applicants must include a dedicated Milestones sub-section to provide a set of discrete benchmarks that will allow unequivocal determination of the progress made towards the goals of the project. Milestones should be scientifically justified and well defined for each year of the project. Whenever feasible, milestones should provide quantitative benchmarks for comprehensively assessing the annual progress of the projects. Milestones must not be simply a restatement of the specific aims. Rather, the milestones should offer a timeline and a pathway for the testing of a discovery concept or development of a technology. These milestones will be used to judge the success of the proposed research on an individual-project basis and evaluate the criteria for the program. Applications that lack milestone information will be considered non-responsive. Non-responsive applications will not be reviewed.

Examples of Milestones:

• Verify that the designed composite nanoparticles are able to reproducibly release an activated component at tumor/cancer cell sites in vivo.
• Ascertain that a new targeted nanoparticle can specifically deliver a therapeutic agent to the tumor by demonstrating that agent concentration in tumor exceeds at least x times its blood concentration.
• Demonstrate the ability of a nanoparticle diagnostic construct to detect at least x specific proteins in blood (out of y specific proteins proposed) at a femtomolar level.
• Demonstrate the ability of the proposed nanotechnology to achieve 95% rate of capture for circulating tumor cells in blood.

Specific Requirements and Guidance for Translational Projects

Plans for commercialization beyond the scope of the Center award should be included in the Research Strategies for Translational Projects. Reviewers will assess the level of commitment of a for-profit entity to proposed projects in terms of likelihood for successful translation of technologies under investigation to the clinic. In addition, Translational Projects that address the specific goals mentioned below must meet the following indicated requirements:

• Use of well-established FDA-approved chemotherapeutic agents: studies with well-established and FDA-approved chemotherapeutic agents may be proposed, but only as initial proof-of-principle models for novel nanotechnology systems. In such case, proposed studies must include a clearly defined transition to the exploration of the proposed system using other agents;
• Improving therapeutic formulations of FDA-approved chemotherapeutics (e.g., to ameliorate some clinically adverse properties): proposed studies must include proper preclinical evaluation in vivo, including comparison to current FDA-approved standard of care;
• Re-formulation of candidate therapeutics: these studies may include drug formulations with demonstrated anti-tumoral potential that have not reached FDA approval due to their toxicity;
• Nanotechnology for delivery of therapeutic nucleic acids: applicants must either provide preliminary data demonstrating effective delivery of payload nucleic acids into tumor cells in vivo or propose studies to clearly address this aspect under the proposed project;
• Nanotechnology based diagnostic technologies/devices: any claims of improved sensitivity or other clinically-relevant advantages must be supported by appropriate preliminary data obtained using clinical samples. If such data are not available, respective rigorous characterizations must be proposed.

Specific Requirements and Guidance for Basic Research/Discovery Projects

Basic Research/Discovery Projects are expected to develop fundamental knowledge enabling more informed and effective translation. They should allow for the building of knowledge of nanomaterial interactions with biological systems. In addition, Basic Research Projects should meet the following indicated requirements:

• Research Strategies should include a description of how the proposed project will contribute to the understanding of mechanisms required for informed and effective translation;
• In the Significance section, describe clearly how the proposed Basic Research/Discovery Project will support one or more proposed translational goals of the Center relevant to the Center Theme.

Letters of Support: Provide letters of support for any collaborative agreements or subcontracts for each individual Research Project, including letters of for-profit entity support describing their interest and commitment. These letters must be signed by senior institutional officials and must detail the institutional and leadership commitment from the participating institutions. For-profit entities providing support to an individual Research Project should include one letter focused on global commitment to commercialization in the Overall component, and one letter describing commitment to an individual Research Project in the corresponding Research Project component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.
• This item should not be completed here, but must be completed in the Overall component.

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.

Planned Enrollment Report (Research Project)

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

PHS 398 Cumulative Inclusion Enrollment Report (Research Project)

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

When preparing your application in ASSIST, use Component Type Core.

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

Applicants may propose, as needed, appropriate shared research resources, or Cores (e.g., nanomaterials synthesis, physico-chemical characterization, (quantitative) imaging, animal studies). These Shared Resources Cores should serve the needs of at least two of the research projects proposed, and must not duplicate analogous NIH-funded resources already established in the applicant institutions (although supplemental funding to such existing resources may be requested). No more than two Shared Resources Cores may be proposed to support Research Projects (in addition to the required Administrative Core).

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

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Shared Resources Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Shared Resources Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

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

Budget (Shared Resources Core)

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

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

PHS 398 Research Plan (Shared Resources Core)

Specific Aims: Provide the objectives and goals of the Shared Resources Core, indicating which of the projects it will serve.

Research Strategy: For each proposed Shared Resources Core include a brief description of the Core and its operations. Explain the rationale for selecting the methodologies and approaches for the Core (indicate how the proposed core will facilitate at least two of the proposed CCNE Research Projects).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.
• This item should not be completed here, but must be completed in the Overall component.

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.

Planned Enrollment Report (Shared Resources Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (Shared Resources Core)

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

When preparing your application in ASSIST, use Component Type Developmental.

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

SF424 (R&R) Cover (Developmental Program)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project (should be "Developmental Program")
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Developmental Program)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Developmental Program)

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

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

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

Project /Performance Site Location(s) (Developmental Program)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Developmental Program)

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

Budget (Developmental Program)

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

Budget for the planned Pilot Projects must be a minimum of $70,000 in direct costs.

Budget for the whole Developmental Program should not exceed 10% of the entire direct costs of the proposed Center's budget.

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

PHS 398 Research Plan (Developmental Program)

Specific Aims: Provide the objectives and goals for planned Pilot Projects and Auxiliary Projects.

Research Strategy: The Developmental Program is expected to carry the potential to broaden the capabilities of the CCNE long term. Within the characteristics specified below, outline your vision on strategies and mechanisms for developing Pilot Projects and Auxiliary Projects and their evaluation/approval. Briefly describe how the ideas for these projects should be solicited and prioritized within the proposed CCNE. You may indicate potential research directions to consider, but do not propose any specific projects in this section.

Expected characteristics of Pilot Projects and Auxiliary Projects are as follows:

• Plans for Pilot Projects (required). Pilots Projects can be early discovery or translational in nature, and are expected to explore high risk new ideas and emerging opportunities that may contribute to the Center, while enabling the support of primarily junior faculty. Each CCNE applicant team must plan for developing Pilot Projects within the Center. Describe your strategy to ensure the anticipated projects will explore new ideas and emerging opportunities that may contribute to the overall theme of the Center. Outline a specific mechanism for the selection and approval of the Pilot Projects to be established by the leadership of the proposed CCNE in consultation with Project and Core Leaders, and experts external to the CCNE (if applicable). Describe the expected participants and duration of the pilot projects, as well as the planned timeline for soliciting these projects. Potentially, these projects may lead to larger research activities through seeking of separate funding in their later stages.
• Plans for Auxiliary Projects (optional). Auxiliary projects are optional and may be used to support supplementary activities that may enhance the capabilities of the CCNE. Plans for support of auxiliary research activities may be described here. Examples of Auxiliary Projects include, but are not limited to: collaboration with other research groups (from within or outside of the Alliance), capabilities needed for the execution of the CCNE program's goals, but not included in Projects or Cores (for example: additional characterization and manufacturing of nanomaterials, animal studies, fees for consultants).

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.
• This item should not be completed here, but must be completed in the Overall component.

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.

Planned Enrollment Report (Developmental Program)

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

PHS 398 Cumulative Inclusion Enrollment Report (Developmental Program)

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

Part I. Overview Information contains information about Key Dates. 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.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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 emphasis and priority of this FOA are on integrated multi-project research efforts aimed at nanotechnology-based solutions for a significant, clinically relevant cancer problem(s) and providing a path to the clinical translation of these nanotechnology-based solutions. It is essential that a multi-disciplinary approach to address both clinical translation and basic, discovery cancer research is utilized.

Reviewers will provide separate impact scores for the Overall and individual Research Project components. Reviewers will provide individual criteria scores for the Overall and for the Research Projects, but not for the other components. The Administrative Core, Shared Resources Cores, and Developmental Program will receive merit descriptors, not numerical scores. Reviewers will also provide appropriately detailed written critiques for all components of the application.

The overall impact score for the entire CCNE may be higher or lower than the scores for the individual components based on the assessment of whether the whole is greater than the sum of its parts.

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

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

Significance

Does the Center address an important problem or a critical barrier to progress in the field? If the aims of the Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Does the proposed Center demonstrate that nanotechnology can successfully provide a better solution to the Center 'theme' problem, given the other currently available approaches and their limitations? What is the likelihood that the proposed Center will ultimately lead to the development of translational, clinically worthy cancer care applications? Will the anticipated advances significantly benefit the broader field of biomedical nanotechnology applications?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? 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 to this FOA: Are the backgrounds, expertise, and commitments of the PDs/PIs and other key personnel sufficient for the proposed scope of activities and in line with the overall goals of the CCNE? How appropriate is the leadership structure of the proposed CCNE in terms of (a) the overall goals of the CCNE; (b) the coordination of efforts of multiple groups and/or institutions participating in a given CCNE? Is there adequate evidence for the managerial and collaborative capabilities of the proposed CCNE leadership, including successful examples of operating (a) large center projects or programs funded by NIH or other federal agencies; (b) experience in using nanotechnology to address medical research and clinical problems?

Given the composition of the multidisciplinary team, the characteristics of its leaders, the balance of specialties, and any ongoing or past interactions or formal collaborations among the team investigators, will the investigators be able to operate as an integrated team? How optimal will this team be for the model of highly interactive research that depends on productive collaborations?

Innovation

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

Specific to this FOA: How innovative are the proposed Center's approaches to shifting current research or clinical practice paradigms by using nanotechnology? Does the proposed Center demonstrate a strong record of scientific innovation that enables the introduction of new areas of translatable nanotechnology research?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? 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?

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

Specific to this FOA: How clear is the outlined path to forward the goals of the proposed CCNE research beyond the scope of this award, including translation? Based on the outlined strategy, involvement of clinicians, and engagement and collaboration with industrial partner(s), what is the likelihood of successful clinical implementation of Center-derived nanotechnologies in the future?

Environment

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

Integration

What are the levels of scientific and organizational integration of the Center components? To what degree are the proposed projects synergistic (as opposed to self-standing, loosely related projects)? Will the interactions across the individual Research Projects and Shared Resource Cores result in a significant value added outcome?

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 a major scientific impact. For example, a Research Project that by its nature is not innovative may be essential to advance the goals of the Center.

For this particular announcement, projects are expected to go well beyond simple demonstration of new nanotechnology-based therapeutic or diagnostic device features.

Significance

Does the project address an important problem or a critical barrier to progress in the? 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: Does the project use nanotechnology to address an important problem in cancer biology and/or oncology? Does the proposed project demonstrate that nanotechnology can successfully provide a better solution to the problem, given the currently available approaches and their limitations? Does the project fit into the overarching theme of the Center and demonstrate that it is best suited for a center environment?

Investigator(s)

Are the Project Lead(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, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

Specific to this FOA: Are the experience and expertise of the project leader and other researchers and team members appropriate for the project proposed?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing nanotechnology to create novel theoretical concepts, approaches or methodologies, instrumentation, or interventions in cancer? Are these 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?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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?

Specific to this FOA: Are the proposed hypothesis and/or approaches sufficiently supported by convincing preliminary data? In the case of incomplete data from applicants' laboratories, are these gaps adequately and convincingly addressed using all available sources of information?

Environment

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

Milestones

Are the milestones adequately comprehensive and realistic? Will these milestones allow for sufficiently accurate and informative evaluation of the progress of the project proposed?

The Administrative Core will receive a merit descriptor rather than a numerical score; individual criterion scores are not used for this component.

Will the proposed Administrative Core effectively coordinate the efforts within the participating institution(s) and outside interactions at the trans-Alliance level? Are the plans for establishment and the proposed roles of the Center's external advisory panel(s) appropriate? Are the proposed training and outreach activities appropriate, and will they have an impact beyond the project period?

Cores will receive merit descriptors rather than numeric scores; individual criterion scores are not used for this component.

Is the proposed Shared Resources Core well matched to the needs of at least two proposed research projects? Will the Shared Resource Core enhance the capabilities of individual projects served to accelerate translation of nanotechnology based strategies to the clinic? What is the overall quality of the proposed core services? Are adequate quality control processes proposed for the facilities or services provided by the Shared Resources Core (including procedures, techniques, and quality control)? Are there feasible and clear plans for prioritizing the use of Shared Resources Cores, their availability to the proposed projects, and their efficient utilization?

Are the qualifications, experience, and commitment of the Shared Resources Core Director(s) and other key personnel adequate and appropriate for providing the proposed facilities or services? Will the use of core services be cost effective to the program?

The Developmental Program will receive a merit descriptor rather than a numeric score; individual criterion scores are not used for this component.

Are the plans for Pilot Projects (and Auxiliary Projects, if proposed) realistic and sufficient for flexible exploration of new ideas and/or opportunities/needs within the proposed Center? Are the plans for selection and approval of projects appropriate? Is the planned duration of projects sufficient for the exploration of new ideas (and needs, if applicable)?

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

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children

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.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned 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.
• Compliance with resource sharing policies.

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.

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.

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

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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.

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.

These Terms and Conditions of Award apply to all individual CCNE U54 awards. All the awardee institution(s), PDs/PIs, and other key personnel must agree to collaborate on the goals of the CCNE and the entire NCI Alliance for Nanotechnology in Cancer.

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

• Determining and coordinating research approaches and procedures, and analyzing and interpreting research data;
• Coordinating efforts to share data across the Center;
• Providing goals for procedures, protocols, and costs to NCI Program Staff as requested;
• Releasing data and protocols according to the approved plans for timely sharing of research resources and data generated through the award, as agreed upon by the Alliance Coordinating and Governance Committee (CGC) and NCI Program Staff;
• Coordinating and encouraging inter-Alliance collaborations to cross-test novel frameworks and projects proposed by fellow CCNEs;
• Participating in the development of Center Executive Committee and the recruitment of appropriate external experts for a CCNE external advisory panel(s);
• Serving on the CGC: One member of each awarded CCNE (one of the PDs/PIs) is required to serve as member of the CGC (for details see Areas of Joint Responsibility below);
• Interacting with the Alliance advisory committees;
• Participating in the annual PD/PI meeting organized by NCI;
• Participating in the program evaluation process as called upon by NCI Program Director and CGC;
• Accepting and implementing all scientific, practical, and policy decisions approved by the CGC to the extent consistent with applicable grant regulations;
• Participating in the development and evaluation of Pilot and Auxiliary Projects;
• Participating in selection of common animal models for comparative studies across the Alliance;
• Participating in the development of Working Groups supporting the discussion and exchange of ideas across the Alliance;
• Providing information to the NCI Program Director and NCI Project on other aspects of Center operation;
• Being prepared for annual administrative site visits by NCI staff; and
• Providing adjusted annual Center milestones each year to the NCI Program Director.
• 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.

All institutions/organizations participating in a given CCNE will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the CCNE award. Also, Centers are expected to share at least non-proprietary information (e.g., protocols and experimental methodologies) with other Centers and Alliance investigators.

To meet nanomaterial data sharing and deposition needs, nanomaterial characterizations, protocols, and associated publications are expected to be submitted to the caNanoLab data portal directly by awardees. All CCNE investigators are strongly urged to work together to ensure that all relevant data are deposited to caNanoLab (no later than upon publication of findings in scientific journals). At least one scientifically qualified person is expected to be designated as the nanomaterial data sharing coordinator for each Center after an award has been made.

Awardee members of the Alliance will be required to accept and implement policies approved by the CGC to the extent consistent with grant regulations.

Each CCNE award and the entire Alliance program will be periodically evaluated by the NIH. Awardees will be expected to participate in such evaluations.

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 HHS, PHS, and NIH policies.

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

Designated NCI Program staff members will have substantial programmatic involvement as Project Scientists. Specifically, the NCI Project Scientists will:

• Serve as NCI voting members on the Alliance Coordination and Governance Committee (CGC) (for details see Areas of Joint Responsibility below);
• Assist in avoiding unwarranted duplications of effort across CCNEs and other Alliance awardees;
• Help coordinate collaborative research efforts that involve multiple Centers;
• Monitor the operations of CCNEs and make recommendations on overall project directions and allocations of project funds;
• Review the progress of individual Centers and specific activities shared among the Centers;
• Participate in the annual PD/PI meeting organized by NCI;
• Participate as Collaborators to the Alliance investigators in some shared activities, if appropriate;
• Assist the awardees as a resource in stimulating their broader interaction with other NCI and NIH programs to disseminate results and outcomes from the CCNEs and effectively leverage existing NIH/NCI resources and infrastructures; and
• Evaluate the adherence of CCNEs to the approved data sharing plan.

The NCI reserves the right to award reduction or suspension of funds for a CCNE that is unable to meet its milestones.

The substantially involved NCI Project Scientist will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

Additionally, an NCI Program staff member acting as a Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. A Program Official may also have substantial programmatic involvement (as Project Scientist/Coordinator). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.

Areas of Joint Responsibility include:

The Alliance Coordination and Governance Committee (CGC) will serve as the main governing board for the NCI Alliance for Nanotechnology in Cancer program. The committee will consist of the following voting members:

• One representative of each CCNE (one of the Center PDs/PIs, e.g., the corresponding PD/PI);
• Representatives of other awardees funded under the Alliance (i.e., IRCN and T32 training programs). The limit on the number of CGC members representing these two efforts will be set not to exceed the number of PDs/PIs representing CCNEs. Thus the make-up of the CGC will be: 50% CCNE PDs/PIs and the remaining 50% - PDs/PIs of nanotechnology IRCN awards and T32 training programs. The membership of non-CCNE PDs/PIs can be rotated every 18-24 months to provide the opportunity to PDs/PIs of all non-CCNE awards to serve on the CGC committee.
• Two NCI Project Scientists.

Each voting member representing the Alliance awardees will have one vote. Each voting NCI Project Scientist will have one vote.

Two co-chairs of CGC will be named from the members representing the Alliance awardees to coordinate its operation.

In addition, the designated NCI Program Director (who can also act as a Project Scientist) and a representative of the NCI Nanotechnology Characterization Laboratory (NCL) will participate in the activities of the CGC as non-voting members. Additional non-voting members to serve in an advisory capacity may be added to the CGC as needed by a decision of the existing voting committee members. These additional non-voting members may include, as needed, other NCI and NIH Program Staff members and/or Program Staff members from other federal agencies (e.g., Food and Drug Administration [FDA], National Institutes of Standards and Technology [NIST], and/or Department of Defense [DoD]).

CGC may establish advisory or expert sub-committees, as necessary, to ensure the progress of the Alliance. External experts (i.e., non-Alliance members) may be invited to participate in such sub-committees. NCI representatives may serve on any CGC sub-committee as they deem appropriate.

CGC will meet two times a year (at least once in person at the annual PD/PI meeting). All CGC decisions and recommendations that require voting will be based on a majority vote.

Main responsibilities of the CGC will include the following aspects:

• Overall organizational oversight of effort coordination across the CCNEs, IRCN awards, and T32 training programs;
• Review of progress of the research activities across the Alliance and making appropriate recommendations to strengthen activities in certain areas;
• Development of standard research protocols to be used across the Alliance, identifying technology impediments to clinical translation, and developing strategies for sharing technologies and validation results.
• Selection of common animal models (based on tumor types) for comparative studies across the Alliance (a dedicated Alliance expert sub-committee may be formed for this task);
• Development of an appropriate structure of Working Groups to promote the exchange of experiences, protocols, and ideas across the Alliance;
• Review the potential of shared support infrastructure at specific institutions to serve the needs of the investigators across the Alliance;
• Schedule CGC meetings and telephone conference calls as necessary for conducting business;
• Ensure that the Alliance takes advantage of existing NCI and NIH resources and programs;
• Develop and recommend progress report formats for individual CCNEs, IRCN awards, and T32 training programs involved in the Alliance; and
• Schedule and participate in the development of the agenda for the annual PD/PI meeting at which all Alliance investigators will present their scientific progress and future plans.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the GCG 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 Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

In addition to the annual PHS 2590 or RPPR, a detailed interim Center progress report will be required once a year. This report will be required approximately six months after the annual PHS 2590 or RPPR, and should be submitted directly to the NCI Program Director (with a copy to the designated Grants Administration official).

The interim and annual reports will be required to be formatted following standardized guidelines developed by NCI Program Staff and approved by CGC. The required content of the reports may be changed according to programmatic needs based on discussions among the Alliance members, CGC, and NCI.

Should problems arise in the conduct of the study, the NCI may require that the Center awardee submit quarterly reports on progress and fiscal matters.

Site visit reporting. NIH/NCI program staff members will conduct annual administrative site visits. CCNEs will be expected to report on their progress during these annual administrative site visits.

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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

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Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: GrantsInfo@nih.gov

Dr. Piotr Grodzinski
National Cancer Institute (NCI)
Telephone: 301-496-1550
Email: grodzinp@mail.nih.gov

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

Arina Kramer
National Cancer Institute (NCI)
Telephone: 240-276-6327
Email: kramerav@mail.nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.