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

Purpose

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on the inception and early-stage development of highly innovative, molecular and/or cellular analysis technologies with transformative potential. The emphasis of this FOA is on supporting the development of novel capabilities involving a high degree of technical innovation for targeting, probing, or assessing molecular and cellular features of cancer biology. Well-suited applications must offer the potential to accelerate and/or enhance research in the areas of cancer biology, early detection, and screening, clinical diagnosis, treatment, control, epidemiology, and/or cancer health disparities. Technologies proposed for development may be intended to have widespread applicability but must focus on improving molecular and/or cellular characterizations of cancer.

Applications involving an existing technology not yet demonstrated for the proposed cancer-relevant application(s) are also within the scope of this FOA but must involve additional technical modifications and development to allow for the proposed cancer-relevant context of use or some significant question of feasibility exists for achieving the proposed aims. If the research focus for the application involves an existing technology, a clear description of the feasibility risk justifying the use of the R21 mechanism must be included in the application. Applicants are encouraged to reach out to the Scientific/Research Contact below with any questions.

This FOA utilizes the R21 award mechanism for exploratory/developmental projects. The R21 mechanism is suitable for projects that are at their inception, conceptual, or idea-based phase. In this phase, the technical feasibility of the proposed technology or methodology should not yet have been established. Preliminary data are not required but are accepted if available. If preliminary data are sufficient to suggest the feasibility of the approach is established, then consideration should be given to submitting to the companion R33 FOA (RFA-CA-20-018).

This funding opportunity is part of a broader NCI-sponsored Innovative Molecular Analysis Technologies (IMAT) Program.

The IMAT Program

Since its inception in 1998, the IMAT Program has focused on stimulating and accelerating the development, integration, maturation, and dissemination of the most novel and highly innovative technologies in support of cancer research and medicine. Together with the NCI's other technology-focused programs, the IMAT program continues to support the development of tools and methods that enable cancer researchers to make new discoveries, enhance our understanding of cancer etiology and proliferation, improve detection capabilities, develop diagnostic methods and treatment strategies, conduct population-scale studies, address and reduce disparities in clinical care, and assist in clinical decision-making.

The current issuance of the IMAT Program consists of four separate FOAs that cover the following two areas:

• Molecular and Cellular Analysis Technology Development for Cancer Research is intended to support the development of technologies that are novel and potentially transformative to the molecular and cellular analysis of cancer, which may, in turn, accelerate basic or clinical cancer research. Applications must offer novel measurement, probing, or targeting of cancer-relevant targets at the molecular or cellular level.
  • RFA-CA-20-017 (this FOA, R21): Supports an early-stage feasibility study (inception through preliminary development) to demonstrate the core functional capabilities of the proposed technology.
  • RFA-CA-20-018 (R33): Assumes completion of the initial phase of development and supports the advanced development and robust validation of the technology.
• Cancer-relevant Biospecimen Science Technologies is centered on the development and validation of novel technologies to improve or assess the quality of cancer-relevant biospecimens for research or clinical care. Applications must offer novel approaches for procurement, preservation, and/or isolation of proteins, DNA, RNA, and other small molecules from biospecimens or otherwise assess their biological integrity. The emphasis is on reducing the impact of pre-analytical variations in the collection, processing, handling, and preservation of cancer-relevant biospecimens or their derivatives to improve their quality and utility for cancer research or clinical care.
  • RFA-CA-20-019 (R21): Supports an early-stage feasibility study (inception through preliminary development) to demonstrate the core functional capabilities of the proposed technology.
  • RFA-CA-20-020 (R33): Assumes completion of the initial phase of development and supports the advanced development and robust validation of the technology.

Additional information about the IMAT Program and its individual FOAs can be found here.

Specific Research Objectives and Scope of this FOA

The proposed projects must be focused on early-stage development and application of an innovative molecular or cellular analysis technology in a biologically relevant system. In addition, all projects proposed in response to this FOA must involve all of the following general attributes:

• Potential for substantial improvements over current approaches and/or adding qualitatively new research capabilities.
• Offers novel capabilities that may be judged by appropriate experts as potentially transformative to research in laboratory and/or clinical settings, and beyond providing incremental improvements to existing capabilities.
• Rigorous study design with a verifiable approach, which is based on well-defined performance measures (see below for a description of performance measures).

For details on addressing these requirements, see Section IV. Application and Submission Information.

Responsive Technologies and Scientific Scope

Responsive technologies include relevant novel materials, chemical reagents, instrumentation, devices, and associated methods. These technologies may be intended for molecular and/or cellular analyses in vitro, in situ, and/or in vivo (with some exceptions listed below), and may target the needs of basic, diagnostic, translational, epidemiological, and/or clinical cancer research or otherwise address issues associated with cancer health disparities. It must be clear that proposed projects are focused on the development of generally applicable technologies to facilitate research in certain areas (e.g., clinical detection, drug development, biomarker discovery and validation, or epidemiology), NOT on pursuing specific discoveries (e.g., discovery of a novel biomarker or demonstrating efficacy for a novel therapeutic agent) or specific applications (e.g. detection of a known biomarker) in those areas.

Technology development projects in any area of cancer-related research are encouraged provided that the technology proposed meets the requirements stated above, including transformative potential for cancer research. Technologies may target atomic, molecular, sub-cellular, and/or cellular features. At the core of any project must be a novel analysis or targeting capability (encompassing novel devices, materials, or chemical/biochemical approaches). General areas of interest include, but are not limited to, the following:

• Novel technologies to distinguish, assess, and/or monitor cancer stages and progression;
• Novel technologies that may aid the elucidation of basic mechanisms underlying cancer initiation and progression;
• New methods, tools, and procedures that may generally facilitate processes related to early cancer detection, screening and/or cancer risk assessment;
• Technologies that can facilitate and/or enhance molecular analyses in cancer epidemiology (e.g., by allowing for rigorous and/or expeditious collection of various types of relevant data);
• Technologies to facilitate/accelerate the processes of drug discovery or development of generic approaches to improve drug delivery;
• Technologies or tools that may help overcome various barriers in research on the incidence, prevalence, mortality, and burden of cancer among members of underserved populations; and
• Technologies to facilitate the collection of relevant biological data for examining the factors contributing to cancer health disparities (e.g., for cancer sub-types and differences across individuals with diverse racial/ethnic backgrounds).

Non-Responsive Projects

The following aspects/characteristics remain outside the scope of the IMAT Program and this FOA. Applications proposing projects with any of the following characteristics will not be reviewed:

• Pursuit of a biological or clinical hypothesis for which the novelty of the project resides in the biological or clinical question (i.e., traditional biological-hypothesis driven research) and NOT in the novel technical capability being developed;
• Use of existing technologies (for which a proof-of-concept has already been demonstrated in a cancer-relevant biological system) that may be ready for advanced development and validation without substantial further developmental efforts;
• Technologies for whole-body or in vivo imaging;
• Inclusion of clinical trials or toxicology studies beyond those required to demonstrate the capabilities of the technology;
• Biomarker discovery or biomarker validation;
• Development of specific contrast agents (though generalizable contrast agents are allowed);
• Development of drugs or therapies; and/or
• Projects focused primarily on software/informatics solutions, database development, data mining, statistical tools, and computational/mathematical modeling (including those applicable to drug and/or patient responses) with the exception of projects which include software development for embedding in new devices or limited amounts of computational efforts as might be needed to develop new devices or methods.

As there are several unique review considerations for this FOA, applicants must address the requested items outlined for the Research Plan in Section IV.2. Application and Submission Information. An application lacking appropriate performance measures, as determined by the NCI program staff, will not be reviewed.

IMPORTANT NOTE: Researchers uncertain as to whether their intended technology development project meets the requirements of this FOA are encouraged to contact the Scientific/Research Contact listed below.

Alternative Opportunities

Related IMAT FOA: Applicants proposing projects that are beyond questions of feasibility, but still require further development and validation should consider applying to the companion FOA (RFA-CA-20-018) which uses the R33 mechanism. Further development encompasses optimization and scaling of the technology or merging with complementary technologies in an effort to improve the overall functionality. NOTE: Applications proposing to merge complementary technologies without a substantial requirement for further development or a clear need for analytical validation are beyond the scope of the IMAT program solicitations altogether.

Other technology-related funding opportunities. Researchers focusing on new bioinformatics or statistical techniques, tools, and/or software development solutions should consider one of the Informatics Technologies for Cancer Research (ITCR) opportunities or one of the Biomedical Information Science and Technology Initiative (BISTI) opportunities. Researchers who emphasize the assessment of whole-body or in vivo imaging technologies as the primary focus of their projects should contact the Cancer Imaging Program (CIP) for information on appropriate funding opportunities.

Annual Meeting

An annual meeting of all investigators funded through this program will be held to share progress and research insights that may lead to further progress in the development of technologies for cancer research and clinical care for cancer patients. All investigators supported through this FOA are required to attend this meeting each year, lasting 2-3 days, unless otherwise notified by NCI program officials.

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)

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) 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

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Tony Dickherber, Ph.D.
Center for Strategic Scientific Initiatives
National Cancer Institute (NCI)
31 Center Drive, Room 10A33
Bethesda, MD 20892
Telephone: 301-547-9980
Email: dickherberaj@mail.nih.gov

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

Specific Aims: Include a brief sub-section "Statement of Potential Impact" on the expected potential of the proposed technology to transform cancer research and clinical practice. The following questions should be addressed with this statement.

• How is the new capability provided by the proposed technology potentially transformative and why may it be expected to produce an unusually high impact on biomedical research and medicine? (i.e., describe the potentially transformative outcomes that might be realized should this technology be successfully developed)
• If applicable, how will the proposed technology overcome limitations for currently available technologies or alternative approaches? (i.e., provide evidence to substantiate the claim of innovativeness beyond currently available technologies)

Research Strategy: Applicants must address the following required aspects:

• Innovative, Cancer-Relevant Technology. The proposed project must be focused on the initial development and demonstration of a highly novel measurement or targeting capability in a biologically relevant system. The application must describe metrics of success that verify achieving the novel technical capability proposed and its anticipated long-term use to advance cancer research and/or clinical practice. The proposed technology should target unmet needs in basic, preventative, diagnostic, translational, epidemiological, health disparities, and/or clinical cancer research or may have potential for broad use in various fields of cancer research.
• Substantial Improvement and/or New Capabilities. All proposed technologies must offer the potential for substantial improvements over conventional approaches and/or add qualitatively new research capabilities not provided by current technologies.
• Transformative Potential. Define clearly the unmet technical need from the research community being targeted by the technology and describe its anticipated use in laboratory research and/or in clinical settings. Claimed potential impact is expected to be in line with the specific performance measures (next bullet).
• Performance measures. Performance measures are objectively assessable measures for determining targeted performance capabilities. They should be carefully selected and precisely defined, and should clearly detail the expected advantages of the proposed technology relative to existing technologies/approaches. Appropriately targeted performance measures require that the underlying experimental results have been subjected to appropriate statistical analysis, yielding a reasonable level of certainty that the targeted level of performance has been achieved.

Additional Information on Performance Measures

Within 'Research Strategy' there must be a dedicated subsection labeled "Performance Measures". Performance measures should be well-described, quantifiable, and scientifically justified. Critical components for proposed measures include the numerically described target of performance as well as the means by which it will be assessed. Performance measures will be a means of judging the success of the R21 project for demonstrating that key feasibility gaps have been overcome, thereby justifying support for further developmental effort (e.g., under a future R33 project). Note that proof-of-principle goes beyond a single observation, so where appropriate, proposed measures should include the relevant statistical context of assessment. Whenever appropriate, present the proposed measures in the context of current technologies to substantiate the anticipated transformative potential. All performance measures should be described within the context in which they would be assessed, statistical strength of the resulting measures, and the approach by which they will be determined.

Specific aims may not be regarded as performance measures. The specific aims describe the goals and intended path of the research. Performance measures provide the means for objectively assessing progress against those aims and substantiate the potential impact the technology might have on cancer research or clinical care. The project will be evaluated for success based on the completion of the performance measure proposed. For some specific aims, it may be sufficient to define a single performance measure. For others, multiple performance measures may be more appropriate.

An example of a properly described performance measure could be achieving a detection limit of 1 femtogram (fg) of a targeted analyte per microliter or less of a sample with a p-value <0.05 under conditions a, b and c, and with 95% confidence limits +/- 0.2 fg for a 2 fg reading over a concentration range of g to h. Other types of performance measures might include:

• Detection of a single targeted cancer cell in 109 normal cells, with false-positive detection rate <2%;
• Demonstration that the measured analyte is highly correlated (Pearson correlation coefficient r >0.95) for a given human serum sample when analyzed on different days. This should include mean, standard deviation, and relative standard deviation for repeatability targets superior to next best approach (if applicable);
• Reduction of sequence read errors to one in 5,000,000 base pairs; and/or
• Demonstration that the technology can be n-fold faster, or n-fold more sensitive, or n-fold more specific, etc, than the current "gold standard" technology.

Please note these additional performance measure examples should still be properly described in an experimental context as demonstrated in the example above.

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.

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 and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive 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.

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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 for this FOA: Are the expectations in that area realistic and in line with the planned developmental efforts? Do the proposed milestones support a transformative capacity for a cancer-relevant field of research or clinical care? Does the proposed technology have the potential to be widely adopted by the relevant research community?

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 for this FOA: Will the proposed technology offer new possibilities for cancer research or clinical care relative to the current methods? If the project focuses on a new cancer-relevant application of an existing technology, how innovative is the proposed new type of technology usage?

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?

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?

Performance Measures

Are the proposed performance measures adequate relative to the specific requirements defined in the FOA? Are they sufficiently realistic? Will the proposed measures allow determination of whether or not the specific aims of the R21 project have been accomplished? Would meeting the proposed measures be sufficient to establish the feasibility of the proposed technology and serve as a foundation for next phase developmental efforts (such as a future R33 project or equivalent)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 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

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.

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 NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

• 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.

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.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.

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 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.

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

Tony Dickherber, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-547-9980
Email: dickherberaj@mail.nih.gov

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

Dawn M. Mitchum
National Cancer Institute
Telephone: 240-276-5699
Email: Dawn.Mitchum@nih.gov

Section VIII. Other Information