Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	Early-Stage Innovative Molecular Analysis Technology Development for Cancer Research (R21)
Activity Code	R21 Exploratory/Developmental Research Grant
Announcement Type	Reissue of RFA-CA-13-001
Related Notices	January 8, 2015 - This PA has been reissued as RFA-CA-15-002. June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
Funding Opportunity Announcement (FOA) Number	RFA-CA-14-003
Companion Funding Opportunity	RFA-CA-14-004, R33 Exploratory/Developmental Grants Phase II RFA-CA-14-005, R21 Exploratory/Developmental Grant RFA-CA-14-006, R33 Exploratory/Developmental Grants Phase II
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.393, 93.394, 93.395
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on the inception and development of early stage, highly innovative, technologies for the molecular or cellular analysis of cancer. Emerging technologies with significant transformative potential that have not yet been explored in a cancer-relevant use may also be considered. An emerging technology is defined (for the purpose of this FOA) as one that has passed the initial developmental stage, but has not yet been evaluated within the context of cancer-relevant use intended in the application and requires significant modification for the proposed application to establish feasibility. The emphasis of this FOA is on molecular analysis technologies with a high degree of technical innovation with the potential to significantly affect and transform investigations exploring the molecular and cellular bases of cancer. If successful, these technologies would 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 be based on molecular and/or cellular characterizations of cancer. This funding opportunity is part of a broader NCI-sponsored Innovative Molecular Analysis Technologies (IMAT) Program.

Posted Date	December 20, 2013
Open Date (Earliest Submission Date)	January 20, 2014
Letter of Intent Due Date(s)	January 20, 2014; April 20, 2014; August 18, 2014
Application Due Date(s)	February 20, 2014; May 20, 2014; September 18, 2014, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June/July 2014; October/November 2014; February/March 2015
Advisory Council Review	October 2014; January 2015; May 2015
Earliest Start Date	December 2014, April 2015; July 2015
Expiration Date	September 19, 2014
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

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

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on the inception and development of early stage, highly innovative, molecular analysis technologies or emerging technologies with significant transformative potential that has not yet been explored in a cancer-relevant use.

Definition of Emerging Technology. An emerging technology is defined (for the purpose of this FOA) as one that has passed the initial developmental stage, but has not yet been evaluated within the context of a cancer-relevant intended use and requires significant modification for the proposed application or otherwise involves a substantial question of feasibility. If the research focus for the application involves an emerging technology, the feasibility risk justifying use of the R21 mechanism must be included.

FOA Emphasis. The emphasis of this FOA is on technologies with a high degree of technical innovation with the potential to significantly affect and transform investigations exploring the molecular and cellular bases of cancer. If successful, these technologies would accelerate and/or enhance research in the areas of cancer biology, early detection, screening, clinical diagnosis, treatment, control, epidemiology, and/or cancer health disparities. Technologies proposed for development may be intended to have widespread applicability but must be based on molecular and/or cellular characterizations of cancer. This funding opportunity is part of a broader NCI-sponsored Innovative Molecular Analysis Technologies (IMAT) Program (http://innovation.cancer.gov/).

This FOA utilizes the R21 award mechanism for exploratory/developmental pilot projects. The R21 mechanism is suitable for projects that are at their inception, conceptual, or idea-based phase. In this phase, technical feasibility of the proposed technology or methodology may 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-14-004).

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 large population 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 three areas:

• Innovative Molecular Analysis Technology Development for Cancer Research (this FOA, RFA-CA-14-003, using the R21 funding mechanism), which is intended to support research projects that are centered on the inception and preliminary development of highly innovative molecular analysis technologies with potentially high impact on cancer research;
• Emerging Molecular Analysis Technology Development for Cancer Research (RFA-CA-14-004, using the R33 funding mechanism), designed to support further development (beyond the initial phase) of emerging molecular analysis technologies that have the potential to be transformative when used for cancer research and/or in cancer-relevant clinical care; and
• Innovative and Applied Emerging Technologies in Biospecimen Science 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. Specifically, tools to improve the isolation and/or preservation of proteins, DNA, RNA and other small molecules from biospecimens or otherwise assess their biological integrity. The emphasis is on issues related to 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 patient clinical care.
• RFA-CA-14-005 (R21): Supports an early-stage feasibility study (inception through preliminary development) to demonstrate core functional capabilities of the proposed technology.
• RFA-CA-14-006 (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 at http://innovation.cancer.gov.

The proposed projects must be focused on the initial development and application of an innovative molecular 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 conventional approaches and/or adding qualitatively new research capabilities not provided by current technologies.
• Transformative Potential. The emphasis of the IMAT program is on technologies that have significant potential to transform research in laboratory and/or clinical settings.
• Rigorous, Verifiable Approach (based on well-defined, quantitative milestones).

For details on addressing these requirements, see Section IV.2. Content and Form of Application Submission.

Responsive technologies include relevant techniques, tools, 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 cancer health disparities. However, it must be clear that proposed projects are focused on the development of generally applicable technologies to facilitate research in certain areas (e.g., drug development, biomarker discovery and validation, or epidemiology), NOT on pursuing specific discoveries in those areas.

Projects in any area of cancer-related technology 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 cellular levels of detection and/or analysis. At the core of any project must be a novel molecular analysis technology (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 relevant types of 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).

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

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 resides in the biological or clinical question (i.e., traditional biological-hypothesis driven research);
• Use of existing technologies (for which a proof-of-concept has already been obtained) that may be ready for the targeted applications without substantial further developmental efforts;
• Technologies for whole-body or in vivo imaging methods;
• 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;
• 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 take care to address the requested items outlined for the Research Plan in Section IV Application and Submission Information: Content and Form of Application Status...

Related IMAT FOA: Applicants proposing projects that are for the advanced stage of development and validation of an emerging technology, rather than pilot projects, should consider applying to the parallel FOA (RFA-CA-14-004) that uses the NIH R33 mechanism.

Other technology-related funding opportunities. Researchers focusing on new bioinformatics or statistical techniques, tools, and/or software solutions should consider one of the Informatics Technologies for Cancer Research (ITCR; http://itcr.nci.nih.gov) opportunities or one of the Biomedical Information Science and Technology Initiative (BISTI; http://bisti.nih.gov) 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; http://imaging.cancer.gov/) for information on appropriate funding opportunities.

An annual 2-day 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.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New Resubmission to this FOA or a prior issuance of this FOA The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NCI intends to fund an estimate of 22 awards, corresponding to a total of $5,000,000, for fiscal year 2015. Future year amounts will depend on annual appropriations.
Award Budget	Direct costs are limited to $500,000 over a 3-year period, with no more than $200,000 in direct costs allowed in any single year. Application budgets must reflect actual needs of the proposed project.
Award Project Period	The total project period request may not exceed 3 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Applicant Organizations

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

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

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

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

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

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

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

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

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

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

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

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

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

The letter of intent should be sent to:

Tony Dickherber, Ph.D.
Center for Strategic Scientific Initiatives, Office of the Director
National Cancer Institute, NIH
31 Center Drive, Room 10A33
Bethesda, MD 20892
Telephone: (301)547-9980
Email: [email protected]

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

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

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

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

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

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

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

Specific Aims: 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.

• How is the 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 application(s) that might be realized should this technology be successfully developed)?
• How will the proposed technology be superior to currently available technologies? What concrete evidence can be provided 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 application of an innovative molecular analysis technology in a biologically relevant system. The application must describe metrics of success that determine or optimize technical capability and its anticipated long-term use to advance cancer research and/or clinical practice. The proposed technology may be targeted for the needs of 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 novelty of the proposed technology and describe its anticipated use in laboratory research and/or clinical settings. Claimed potential impact is expected to be in line with the specific quantitative milestones (next bullet).
• Quantitative Milestones. Quantitative Milestones 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 quantitative milestones assume that the underlying experimental results have been subjected to the appropriate statistical analysis, yielding a minimum level of certainty that the targeted level of performance has been reached.

Additional Information on Quantitative Milestones

"Milestones" must be addressed in a dedicated subsection of Research Strategy with that title. Milestones should be well described, quantitative, and scientifically justified. Both the numerical performance targets as well as the means by which they will be assessed are critical components sought with regards to quantitative milestones. Discuss the milestones as a means of judging the success of the R21 project as well as providing proof-of-principle for justifying further developmental effort (e.g., under a future R33 project). Note that proof-of-principle goes beyond a single observation, so where appropriate, milestones should include the relevant statistical context for the targeted parameter. Whenever appropriate, present the proposed milestones in the context of current technologies to substantiate the anticipated transformative potential. All milestones 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. All milestones should be listed in a single location near the end of the research strategy section to aid review of the application.

Specific aims may not be regarded as milestones. The specific aims describe the goals and intended path of the research. Quantitative milestones provide a numerical target of performance or capability for judging how realistic the proposed goals are and what potential impact the technology might have on cancer research. Later, milestones will allow one to determine whether the project has been successfully completed and reached the specified quantitative goals. Thus, proper quantitative milestones are expected to include context/project-relevant numerical specifications (such as sensitivity and specificity of a technology/procedure, or a count of some desired or newly discovered molecule, or some other quantifiable metrics of performance). For some types of specific aims, it may be sufficient to define a single milestone. For other types, multiple milestones may be more appropriate.

An example of a properly described quantitative milestone could be achieving a detection limit of 1 fg or less with a p value < 0.05 under conditions a, b and c, over a range from p to q, and with 95% confidence limits +/- 0.2 fg for a 2 fg reading over the whole range. Other examples of quantitative milestones might include:

• Detection of one cancer cell in 108 normal blood cells;
• Detection of a target analyte at a concentration of 1 fmol in serum;
• 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;
• Detection of one mutated gene in the presence of 1,000,000 wild-type copies;
• Demonstration that the technology gives the same result in 95 out of 100 assays; and/or
• Demonstration that the technology can be n-fold faster (or n-fold more sensitive, or less expensive, etc.) than the current "gold standard" technology.

An application lacking quantitative milestones as determined by the NCI program staff will not be reviewed.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

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

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

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

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

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). 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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

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 focus their evaluation on 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.

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

In addition, specific for this FOA: What is the potential of the proposed technology to transform cancer research or clinical practice if the project is successfully completed? 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 New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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?

In addition, specific for this FOA: How innovative is the proposed technology? Does the proposed technology offer clear and significant improvement over currently available methods and platforms? Will the proposed technology offer new possibilities for cancer research or oncological practice 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? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

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

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?

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

Milestones

Are the proposed quantitative milestones adequate relative to the specific requirements defined in the FOA? Are they sufficiently realistic? Will the proposed milestones allow determination of whether or not the specific aims of the R21 project have been accomplished? Would meeting the proposed milestones 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

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

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

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

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

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

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: [email protected]

Tony Dickherber, Ph.D.
National Cancer Institute (NCI)
Tel: 301-547-9980
Email: [email protected]

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

Heather Weiss
National Cancer Institute (NCI)
Telephone: 240-276-6318
Email: [email protected]

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

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