Part 1. Overview Information

Key Dates

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

P?urpose

The purpose of this funding opportunity announcement (FOA) entitled "Toward Translation of Cancer Nanotechnology Interventions (TTNCI)" is to enable the translation of nanotechnology-based cancer interventions relying on next-generation nanoparticle formulations and/or nano-devices. Successful TTNCI projects will mature nanotechnology-based interventions that possess a strong potential to improve cancer diagnosis and/or treatment efficacy. The outcomes of TTNCI-supported projects should aid the development of mature nanotechnology interventions with efficacy exceeding the current standard of care for a given cancer indication. It is expected that successful TTNCI-supported projects, upon their completion, can qualify for Good Manufacturing Practice (GMP) materials synthesis and/or device fabrication and Good Laboratory Practice (GLP) and successfully compete for NCI Experimental Therapeutics (NExT) program and other NCI translational programs to continue a path towards the clinic. Projects supported by the TTNCI initiative will incorporate multi-disciplinary research in biology/oncology, chemistry, physics, and/or engineering.

Nanotechnology in the context of this FOA. To be appropriate for this FOA, the proposed nanotechnology approaches, materials, devices, and technologies should meet the following criteria:

• The functional or active component(s) 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.

Nanoparticles and nano-devices that are/were in clinical trials. For nanoparticle constructs or nano-devices that are already in clinical trials, the proposed TTNCI project should involve a different interventional approach than one investigated under the current/prior clinical trial.

This FOA will NOT support projects that:

• Propose nano-formulations utilizing traditional liposomes similar to those that have been approved by the FDA or are currently in clinical trials;
• Involve discovery stage research on nanotechnology-based platforms with little to no prior evidence-based research;
• Involve clinical trials or in vivo studies in human subjects;
• Propose only the use of naturally-occurring materials (e.g., polysaccharides, proteins, viruses) that are not specifically engineered or modified for the intended function;
• Focus on nanotechnology solutions for AIDS/HIV in the context of cancer.

Background

Potential of nanotechnology-based cancer interventions. Significant progress has been made in the synthesis and characterization of engineered nanoparticles and nano-devices for diagnosis and treatment of cancers and many cancer nanotechnology strategies have already moved into clinical trials and obtained FDA approval. The early development of nanomedicines has been conservative, selecting well-established nanoparticle constructs (i.e. liposomes) and combining them with FDA-approved small molecule drugs. Currently, efforts to encapsulate two or more drugs into one nanoparticle for their synergistic action as well as the use of other APIs such as nucleic acids, peptides, and antibodies are also being investigated. In parallel, materials scientists are studying a wide range of nanoparticle designs, possessing various mechanical, magnetic, optical, and biochemical properties. Such particles could perform not only as cargo (API) delivery vehicles, but also can contribute to improving treatment efficacy due to their material properties and structural design. Similarly, diagnostic strategies relying on in vivo imaging nanoparticles or in vitro nano-devices are being used for early disease detection, surgery assistance, and patient stratification to enhance treatment outcomes. Overall, these novel nanoparticle and nano-device designs combined with innovative therapeutic and diagnostic strategies have the potential to improve the effectiveness of nanotechnology interventions and integrate them into mainstream cancer care.

NCI has been supporting the development of nanotechnology for cancer using a multitude of funding mechanisms (http://nano.cancer.gov). The information on general areas of research interests and status of these activities, can be found in the following documents:

• Strategic Workshop on Cancer Nanotechnology recently held at NCI (the workshop's report can be found at https://www.ncbi.nlm.nih.gov/pubmed/31240914);
• Summary of outcomes of the NCI Alliance for Nanotechnology in Cancer program (publication can be found at https://www.ncbi.nlm.nih.gov/pubmed/31257722);
• NCI Cancer Nanotechnology Plan (caNanoPlan) (see https://www.cancer.gov/nano/research/plan);

The research community recognizes the importance of further support for translation of nanotechnology-based interventions and expects that, in the future, nanotechnology will become a significant part of clinical oncology.

Research Objectives for TTNCI Awards

General Expectations for TTNCI Projects. TTNCI awards are expected to produce advances in translational readiness of nanotechnology-based cancer interventions. Significant advances are expected to be achieved in the overall capacity for employing these interventions as clinically viable cancer diagnostics and/or therapeutics. Each proposed TTNCI project is expected to focus within one or more of three selected areas: 1) Combination therapy, 2) Immunotherapy, and 3) Imaging and Diagnostics.

By the end of the project, funded technologies should mature sufficiently to qualify for GMP materials synthesis and/or device fabrication and GLP evaluation studies and be well-positioned to compete for NCI translational programs including the NExT program.

Possible Research Directions. Examples of appropriate research areas are listed below. These examples are not meant to be comprehensive. Additional research foci are also encouraged, providing they are consistent with the general expectations stated above. For further details, see Section IV.2. Content and Form of Application Submission.

Research priorities of the proposed program were selected based on clinical challenges where nanotechnology has displayed a unique potential solution, as compared to other contemporary approaches. These priority areas include: 1) Combination Therapy, 2) Immunotherapy, and 3) Imaging and Diagnostics.

Combination Therapy

• Expand the repertoire of delivered molecules;
• Re-formulate highly potent, yet toxic drug loads;
• Deliver two or more synergistic APIs in precise ratios;
• Deliver radionuclide for nanoparticle-based radiation therapies;
• Combine unique treatment modalities.

Immunotherapy

• Deliver combinations of antigens and adjuvants;
• Reverse immune-suppression;
• Utilize nano-diagnostic tools to understand low response rates.

Imaging and Diagnostics

• Enable and validate multi-modal imaging agents for in vivo diagnostic purposes;
• Develop intra-operative imaging techniques;
• Develop and validate in vitro nano-devices for improved cancer diagnosis and therapy outcome monitoring;
• Combine diagnostic and therapeutic modalities into a multifunctional theranostic intervention strategy;
• Stratify patients to improve treatment outcomes.

Tumor Types. All TTNCI 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.

Annual Principal Investigators' Meeting

NCI holds an annual meeting of investigators funded through institute's nanotechnology programs with the purpose of sharing research progress and establishing collaborations. All investigators supported by this FOA are expected to attend this two-day meeting organized by NCI each year.

Additional Available Resources

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 NCI’s Nanotechnology Characterization Laboratory (caNanoLab) provides 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 sponsors the cancer Nanotechnology Laboratory data portaland the National Cancer Informatics Program (NCIP) Nanotechnology Working Group. The caNanoLab is designed to facilitate sharing of nanomaterials data and to expedite and validate the use of nanomaterials in medicine.
• Animal models. NCI supports a broad spectrum of animal facility experimental resources (Laboratory Animal Science Program [LASP]). It also operates the Center for Advanced Preclinical Research [CAPR] 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.
• NCI Experimental Therapeutics (NExT) program. The NCI Division of Cancer Therapy and Diagnosis (DCTD) operates the NExT Program to advance clinical practice and to bring improved therapies to patients with cancer. The NExT Program is not a grant mechanism; awardees do not receive direct funding; rather, the NCI may allocate various contract and grant resources toward the implementation and development of submitted projects. Successful applications need to describe a clear path to the clinic and potential benefit to patients.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

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

• 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) 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) 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 to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active 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.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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.

2. Content and Form of Application Submission

Facilities and Other Resources:

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

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).

Significance

Project Scope and Emphasis. The proposed project should describe advanced pre-clinical development of nanotechnology-based cancer intervention relying on next-generation nanoparticles (non-liposomal) or nano-devices with strong potential to improve treatment and/or diagnosis effectiveness. It should also provide rationale for the clinical potential of described nanotechnology-based strategy.

Innovation

In the Innovation sub-section, provide a comparison of the proposed nanotechnology-based intervention approach to available or possible classical approaches/options and/or currently used nanotechnology solutions. Discuss the potential advantage of the proposed approach and provide data (either preliminary data from the laboratory of the investigators or literature data) supporting this advantage.

Approach

In the Approach sub-section, provide information pertaining to the following requirements.

1. Well Developed, Rigorous Project. Proposed projects are expected to be conceptually well developed and well supported by appropriate preliminary data from investigators laboratories with appropriate alternative strategies. The preliminary data should demonstrate the efficacy of the proposed intervention in at least two animal models (in case of proposed therapeutic or in vivo diagnostic strategies) and/or experiments involving human samples (in case of proposed in vitro diagnostic strategies). The scope of the proposed project should include physicochemical characterization, biodistribution, safety pharmacology, toxicokinetic/toxicodynamic studies, and additional efficacy confirmation studies in appropriate animal models (see section below: Selection of Animal Tumor Models). Furthermore, the proposed work should enable advanced optimization of the synthetic routes and process chemistry for proposed nanomedicines or fabrication processes for nano-devices. It is expected that by the end of the project, proposed technologies should mature sufficiently to qualify for GMP materials synthesis and/or device fabrication and GLP evaluation studies.

2. Interaction with the NCI's Nanotechnology Characterization Laboratory (NCL). The investigators are strongly encouraged to work closely with NCL during their project and submit the initial batches of their nanomedicines for confirmatory physicochemical and biological characterization at the early stages of the project.

3. 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, TTNCI applicants are strongly encouraged to consider cancers that may strongly 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), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and Cancer Genome Characterization Initiative (CGCI). Additionally, applicants should consider the tumor type relative to its existing treatment and/or diagnostic paradigms and how their proposed approach could improve these for the tumor type or respective indication.

4. Selection of Animal Tumor Models. Describe the animal tumor models to be used in the proposed studies and explain why selected models carry the potential to predict the behavior in human subjects. The use of non-rodent species (large animals) in proposed studies is strongly encouraged, although not required;

5. 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 TTNCI funding opportunity 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.

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. The milestones should provide the means for assessing the progress made towards each aim and offer a timeline for it. The completion of these milestones will be used to judge the success of the proposed research on an individual project basis.

Examples of Milestones:

• Assess the biodistribution of nanomedicine delivery to different organs by calculating the ratio of accumulation in tumor vs other organs
• Quantify (and compare among different animal models, when applicable) dose-effect relationship
• Quantify blood circulation half-life of proposed nanomedicine and compare it with half-life of its 'free' counterpart
• Demonstrate that nanotechnology diagnostic imaging agent can resolve "x" cancer cells
• Demonstrate the ability of a diagnostic construct to detect at least x specific proteins in blood with "y" sensitivity.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The Data Sharing Plan should address the sharing of nanomaterials data through the caNanoLab data portal. At least one scientifically qualified person is expected to be designated as the nanomaterial data sharing coordinator for each TTNCI project after an award has been made. All applications are expected to submit data to caNanoLab upon publication. Please refer to https://wiki.nci.nih.gov/display/caNanoLab/caNanoLab+and+Data+Sharing for appropriate text

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 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.

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

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.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) 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.

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The emphasis and priority of this FOA are on advancing translational readiness of nanotechnology-based cancer interventions. The priority will be given to innovative projects in advanced pre-clinical stage which use next generation nanoparticles or nano-devices for the development of clinically viable cancer interventions carrying strong potential of improving cancer treatment or diagnosis effectiveness.

Significance

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

Specific to this FOA: What is the clinical potential of the proposed nanotechnology-based cancer intervention?

Investigator(s)

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

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 is the use of proposed nanotechnology approach as compared to other available approaches for addressing the clinical problem described in the application? What is the innovation potential of the proposed project in terms of overcoming major barriers towards producing an effective and improved cancer treatment and/or diagnosis for the clinical problem described in the application?

Approach

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

Specific to this FOA: Are the proposed approaches sufficiently supported by convincing preliminary data? How strong is the supporting evidence that the proposed nanotechnology approach may produce a better clinical outcome than other available approaches for the problem addressed?Does the presented data indicate potential for improved treatment and/or diagnosis effectiveness in the described clinical problem? Will the study methodologies described in the project advance the maturity of the proposed nanotechnology-based cancer intervention to qualify for GMP materials synthesis and/or device fabrication and GLP evaluation studies by the end of the project?

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

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?

M?ilestones

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

Not Applicable

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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.

• 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.

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

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

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.

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

2. Administrative and National Policy Requirements

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.

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.

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 https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://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 https://www.hhs.gov/civil-rights/for-individuals/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.htmlor 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.

3. Reporting

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 agreementsare 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.

Section VII. Agency Contacts

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

Piotr Grodzinski, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3305
Email: grodzinp@mail.nih.gov

Mark G Caprara, PhD
Center for Scientific Review (CSR)
Telephone: 301-827-3076?
Email: capraramg@mail.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

Section VIII. Other Information