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

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

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

The purpose of this funding opportunity announcement (FOA) on Innovative Research in Cancer Nanotechnology (IRCN) is to expand the fundamental understanding of the processes pertinent to the use of nanotechnology in cancer. The goal of IRCN projects is to generate new fundamental knowledge associated with the development of nanotechnology-based solutions to major problems in cancer-biology and/or oncology. The outcomes of IRCN-supported projects should inspire and aid the ultimate development of innovative, clinically relevant nanotechnology solutions for cancer (although prospective clinical translation of the IRCN findings remains beyond the scope of this FOA). Projects supported by the IRCN initiative should incorporate multidisciplinary research efforts in biology/oncology, chemistry, physics, and/or engineering.

The IRCN initiative is a part of the NCI Alliance for Nanotechnology in Cancer program. In addition to IRCN projects supported by this FOA, the Alliance consists of the Centers of Cancer Nanotechnology Excellence (CCNEs, supported by the U54 mechanism) and T32 training programs (supported through PA-16-152).

Nanotechnology in the context of this FOA. To be appropriate for 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.

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.

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 NCI through support of multidisciplinary research under the umbrella of the NCI Alliance for Nanotechnology in Cancer, 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 continues to support 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 nanotherapeutics, 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);
• a Request for Information (NOT-CA-13-017); and
• a Cancer Nanotechnology Plan (caNanoPlan) published in 2015 (a copy can be found at https://nano.cancer.gov/about/plan).

The research community including 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 recognizes the importance of further investigations into fundamental understanding of interactions between nanoparticles and/or nanodevices and biological systems, and views them as key support to informed and successful technology translation.

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.

The continued Alliance program consists of the following initiatives:

• Centers of Cancer Nanotechnology Excellence (CCNEs). CCNE teams (funded through the U54 mechanism) are 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 contribute to the understanding of clinically relevant cancer problems.
• Innovative Research in Cancer Nanotechnology (IRCN, covered by this FOA) Awards. IRCN awards support smaller, well-defined projects aimed mainly at discovery research. Their focus is to develop further understanding of nanomaterial and/or nanodevice interactions with biological systems and the mechanisms of nanoparticle and/or nanodevice delivery to the desired and intended cancer targets in vivo. IRCNs serve as an avenue to infuse the Alliance with new approaches and expertise in both nanotechnology and cancer.
• Interdisciplinary Nanotechnology Training and Career Development. To enhance multidisciplinary training, T32 training programs dedicated to cancer nanotechnology are supported through the Parent T32 Announcement PA-16-152. As defined in NOT-CA-14-035, the NCI participates in this NRSA T32 program to further accelerate and intensify the development of a workforce highly skilled in nanotechnology research with medical applications.

General Expectations for IRCN Projects. IRCN awards are expected to produce advances in applying nanotechnology to cancer research: Significant advances are expected in the overall capacity to employ nanotechnology to understand neoplastic diseases. Each proposed IRCN project is expected to generate new fundamental knowledge aiding the development of nanotechnology-based solutions to major problems in cancer-biology and/or oncology. These projects should emphasize fundamental understanding of nanomaterial and/or nanodevice interactions with biological systems, including aspects relevant to the delivery of nanoparticles and/or nanodevices to desired and intended cancer targets in vivo. The innovative use of nanotechnology to solve cancer biology/oncology problems is viewed as more significant than innovation in nanotechnology itself (e.g., development of new nanomaterials).

Possible Research Directions. Examples of appropriate research areas are listed below. These examples are not meant to be comprehensive. Additional directions are also encouraged, providing they are consistent with the general expectations stated above.

• Detailed studies and understanding of nanoparticle and nanodevice delivery mechanisms and implications of systemic distribution, including, but not limited to:
• factors affecting endosomal escape of nanoparticles;
• Enhanced Permeability and Retention (EPR) effect;
• comparison of passive vs active targeting;
• evidence of nanomaterial penetration through biological barriers and target organ accumulation with minimal off-target effects;
• Techniques and tools to overcome failure of therapy, including, but not limited to:
• acquired drug resistance;
• presence of circulating tumor cells (CTCs);
• the establishment of metastatic spread;
• Tools and devices aimed specifically at monitoring of the tumor microenvironment, its heterogeneity, and its changes during tumor progression;
• Understanding and refinement of next generation nanosystem design (e.g., bioresponsive and bioactivatable nanomaterials, externally triggered nanoparticles/nanosystems, physiologically triggered nanoparticles/nanosystems);
• Approaches to further understanding and effectiveness of cancer immunotherapies, including, but not limited to:
• vehicles for delivery of vaccines and adjuvants;
• artificial antigen presenting cells;
• tools for post-treatment monitoring of the immune system;
• Technologies suitable for biomarker discovery and screening (e.g., devices that detect and monitor changes in biomarker expression);
• Development of improved multi-biomarker detection and/or diagnostic devices (e.g., fundamental studies of nanomaterial properties that affect sensitivity and specificity of cancer-specific biomarkers);
• Diagnostic nanoparticles/devices that preserve integrity of captured cells and conformation of isolated molecules for downstream activity assays and analyses;
• Technologies for cancer molecular targeting, discovery, and validation (e.g., targeting of signaling pathway members such as mutant KRAS or mTOR);
• Devices and tools capable of penetrating cellular and/or physiological barriers (e.g., blood-brain-barrier, stroma);
• Integration of modeling and simulation approaches that incorporate characterization data on interactions of nanoparticles with the physiological environment to guide rational nanomaterial design.

Tumor Types. All IRCN applicants are expected to concentrate their proposed efforts on one or two 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.

An annual meeting of investigators funded by the Alliance program is held to share research progress and to aid in the development of nanotechnologies for cancer research and care. All investigators supported by this FOA are required to attend this three-day meeting organized by NCI each year.

As the efficiency of the funded research is an increasing priority for NCI, IRCN awardees will be required to participate in an external evaluation process of the Alliance initiative coordinated by NCI Program Staff. The purpose of the evaluation process is to monitor and assess the performance of the IRCN awards in achieving the goals of this FOA. This process includes evaluating the quality and innovation of the research conducted in the IRCN awards, as well as assessing other critical indicators, including collaborations, peer-reviewed publications, patent disclosures and filings, technology commercialization, and resource and data sharing across the Alliance.

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 physicochemical, 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.
• 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. IRCN applicants are encouraged to consider establishing partnerships with other groups, and divisions and programs within NCI that may benefit the IRCN'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), the Cancer Diagnosis Program (CDP; http://www.cancerdiagnosis.nci.nih.gov/), the Cancer Imaging Program (CIP; https://imaging.cancer.gov/), and the Cancer Systems Biology Consortium (CSBC; http://csbconsortium.org/).

Beyond the Alliance and other NCI resources, IRCN 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.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made 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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

Given the need for the integration of multidisciplinary efforts in IRCN projects, applicants are strongly encouraged to take advantage of the multiple PD/PI option with one PD/PI representing biology or oncology fields and at least another PD/PI representing the fields of chemistry, physics, or engineering.

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

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

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

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

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

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

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

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

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

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

Facilities and Other Resources: Under a heading "Nanomaterials Characterization and Animal Resources", provide a description of nanomaterials fabrication/synthesis and characterization facilities, including access to animal studies and the capacity to link to the capabilities of NCI’s Nanotechnology Characterization Laboratory (NCL).

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

All instructions in the SF424 (R&R) Application Guide must be followed. Annual PDs/PIs' Meeting. Applicants must plan appropriate travel funds for the PD(s)/PI(s) and selected members of the research team to participate in the Annual Alliance PDs/PIs' meetings. Budgets should account for the traveling of Key Personnel and other necessary costs. PD(s)/PI(s) are required to attend, while the attendance of others is optional.

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

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

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

Specific Aims: Outline the specific goals of the project.

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

Project Scope and Emphasis. The proposed project should emphasize fundamental understanding of mechanisms associated with the use of nanotechnology in solving a cancer-relevant problem. Under the Significance sub-section, provide rationale for why the proposed project is expected to produce a significant body of fundamental, mechanistic knowledge relevant to the interactions of nanomaterials and/or nanodevices with biological systems and/or the mechanisms of nanomaterial and/or nanodevice delivery to the intended targets in vivo.

Well Developed, Rigorous Project. Proposed projects are expected to be well developed conceptually and, in general, well supported by appropriate preliminary data from investigators laboratories. 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., studies of delivery mechanisms, 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.

Potential for Innovation- 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 the proposed 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.

Selection of Tumor Types. The project may focus, as appropriate and justified, on one or two rationally selected tumor types or types of abnormalities. In selecting specific tumor types, IRCN applicants are strongly encouraged to consider cancers that may benefit from a nanotechnology approach and to take advantage of 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 that you plan to use in the proposed studies.

Possible Research Directions. Examples of appropriate research directions are listed in Section I. The list is not meant to be comprehensive and additional directions/topics are also encouraged, providing they fit into the overall goals of IRCN and conform to other requirements. 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.

Note: Proposed projects may use an appropriate combination of the following types of models in silico theoretical modeling of human systems, sub-cellular systems and established cell lines in vitro, ex vivo clinical biospecimens, and/or in vivo animal models.

Future Collaborations. In the Approach sub-section, identify the areas of research in which you may seek collaborations in the future to expand and complement your proposed efforts. Note that, if possible and appropriate, Alliance awardees will be encouraged and expected to engage in such mutually beneficial collaborations within and outside of the current Alliance Network.

Milestones. This sub-section is required for all applications. All applicants must describe here 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 and be based on the proposed specific aims. Whenever feasible, milestones should provide quantitative benchmarks for comprehensively assessing the annual progress of the project. Milestones must not be simply a restatement of the specific aims. The specific aims describe the research goals of the project. Rather, the milestones should provide the means for assessing the progress made towards each aim and offer a timeline and a pathway for the testing of a discovery concept or development of a technology. The completion of these milestones will be used to judge the success of the proposed research on an individual-project basis.

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.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The Data Sharing Plan should address the sharing of nanomaterial data through the Alliance caNanoLab data portal. At least one scientifically qualified person is expected to be designated as the nanomaterial data sharing coordinator for each IRCN project after an award has been made.

Appendix:

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

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

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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 the development of basic or pre-clinical research projects, addressing major barriers in cancer biology and/or oncology using nanotechnology-based solutions. The priority is for innovative projects with high potential to generate significant new knowledge relevant to fundamental understanding of the processes pertinent to the use of nanotechnology in cancer, including interactions of nanomaterials and/or nanodevices with biological systems and aspects relevant to their delivery to the desired and intended cancer targets in vivo as well as characterization of detection and diagnostic devices in vitro.

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

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

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

Specific to this FOA: How relevant is the project to cancer biology and/or oncology? What is the potential of the proposed project to generate fundamental understanding of the processes pertinent to the use of nanotechnology in cancer? What is the potential of the proposed project to advance significantly the fundamental understanding of nanomaterial and/or nanodevice interactions with biological system in the context of their delivery to appropriate cancer targets in vivo or characterization of detection and diagnostic devices in vivo? If applicable, how strong is the rationale that the proposed nanotechnology approach may be better than other available approaches for the problem addressed?

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

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: If applicable, how innovative is the nanotechnology approach as compared to other available approaches for addressing the cancer biology and/or oncology problem described in the application? What is the innovative potential of the proposed project in terms of overcoming major barriers that currently restrict the effective use of novel nanotechnology solutions towards cancer-relevant problems?

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

Specific 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? Will the study methodologies proposed in the project enable the development of a significant body of new knowledge? Are the multidisciplinary approaches proposed appropriate, well-matched to the nature of the project, and sufficient for optimal and comprehensive addressing of the project hypothesis and/or objectives?

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

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

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

Milestones

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

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

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

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

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

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

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

Not Applicable

Not Applicable

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

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

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

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

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

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

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

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

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

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

Piotr Grodzinski, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-451-8983
Email: [email protected]

Christopher Hartshorn, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3315
Email: [email protected]

Christina Liu, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3348
Email: [email protected]

Mark Caprara, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-827-3076
Email: [email protected]

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

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

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