Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	Research Answers to NCI’s Provocative Questions - Group B (R21)
Activity Code	R21 Exploratory/Developmental Grant
Announcement Type	New
Related Notices	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-13-019
Companion Funding Opportunity	RFA-CA-13-016, R01 Research Project Grant RFA-CA-13-017, R21 Exploratory/Developmental Grant RFA-CA-13-018, R01 Research Project Grant RFA-CA-13-020, R01 Research Project Grant RFA-CA-13-021, R21 Exploratory/Developmental Grant RFA-CA-13-022, R01 Research Project Grant RFA-CA-13-023, R21 Exploratory/Developmental Grant RFA-CA-13-024, R01 Research Project Grant RFA-CA-13-025, R21 Exploratory/Developmental Grant
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, 93.396, 93.399
Funding Opportunity Purpose	The purpose of this Funding Opportunity Announcement (FOA) is to support innovative research projects designed to solve specific problems and paradoxes in cancer research identified by the NCI Provocative Questions initiative. These problems and paradoxes phrased as questions are not intended to represent the full range of NCI's priorities in cancer research. Rather, they are meant to challenge cancer researchers to think about and elucidate specific problems in key areas of cancer research that are deemed important but have not received sufficient attention. Some of these "Provocative Questions" (PQs) stem from intriguing but older, neglected observations that have never been adequately explored. Other PQs are built on more recent findings that are perplexing or paradoxical, revealing important gaps in current knowledge. Finally, some PQs reflect problems that traditionally have been thought to be intractable but that now may be open to investigations using new strategies and recent technical advances. In the second issuance in 2012, there were eight PQs FOAs, each covering a subset of identified PQs and utilizing, respectively, the R01 and R21 funding mechanisms.  The current reissuance of the PQ Program involves an updated set of 20 PQs.  In order to facilitate the peer review process, the new/updated PQs have been divided into five groups related by themes resulting in five R01 FOAs and five R21 FOAs. PQs in each Group are thematically related. However, the order of the groups and numbering of questions within a group are essentially arbitrary and should not be construed to indicate any order of priority. This FOA, using the R21 exploratory/developmental funding mechanism, solicits applications for PQs in Group B. The companion FOA for PQs in Group B, using the R01 funding mechanism, is RFA-CA-13-018. PQs in this group challenge investigators to seek answers to specific unsolved problems generally related to mechanisms of tumor development or recurrence. Each research project proposed in response to this FOA must be focused on solving one particular research problem defined by one specific PQ selected from the list in Group B. Projects proposed to address specific PQs may use strategies that incorporate ideas and approaches from multiple disciplines, as appropriate. Transdisciplinary projects are encouraged as long as they serve the scientific focus of the specific PQ chosen. The other four groups of PQs (and their respective FOAs) are: Group A covered by RFA-CA-13-016 (R01) and RFA-CA-13-017 (R21) that generally relates to cancer prevention and risk; Group C covered by RFA-CA-13-020 (R01) and RFA-CA-13-021 (R21) that generally relates to cancer detection, diagnosis, and prognosis; Group D covered by RFA-CA-13-022 (R01) and RFA-CA-13-023 (R21) that generally relates to cancer therapy; and Group E covered by RFA-CA-13-024 (R01) and RFA-CA-13-025 (R21) that generally relates to clinical effectiveness.

Posted Date	September 30, 2013
Open Date (Earliest Submission Date)	December 15, 2013
Letter of Intent Due Date(s)	30 days before the due date
Application Due Date(s)	January 15, 2014 and June 20, 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	April-May 2014 and October-November 2014
Advisory Council Review	August 2014 and January 2015
Earliest Start Date	September 2014 and March 2015
Expiration Date	June 21, 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

The purpose of this Funding Opportunity Announcement (FOA) is to support new research projects designed to use sound and innovative strategies to solve specific problems and paradoxes in cancer research identified by the National Cancer Institute (NCI) as the NCI’s Provocative Questions (PQs).

This program covers five R01 FOAs and five parallel R21 FOAs. All FOAs for each mechanism are of identical format and general requirements, differing only in specific PQs covered. This FOA solicits applications for smaller, experimental/developmental research projects in response to PQs in Group B using the NIH R21 funding mechanism. The companion FOA, RFA-CA-13-018 is a parallel announcement for larger, well-developed projects in response to PQs in Group B using the NIH R01 mechanism.

To be responsive to this FOA, each application must specifically address a particular scientific problem identified as one of the PQs in Group B listed in this FOA.

The objective of the Provocative Questions Initiative is to stimulate specific areas of cancer research that are understudied, neglected, paradoxical, or have been difficult to address in the past. Both of the previous issuances of PQs FOAs in 2011 and 2012 had been preceded by several NCI-sponsored workshops to identify, articulate, and prioritize particularly compelling but understudied problems in cancer research to create a list of PQs. Following the two FOAs in 2011, eight FOAs were issued in 2012, utilizing, respectively, the R01 and R21 funding mechanisms.

For the current issuance of the PQ Program, the second list of PQs is now updated to a set of 20 PQs. Some of these 20 PQs are new whereas others are refocused relative to the prior lists.  In order to facilitate the peer review process, the new/updated PQs have been divided into five groups (related by PQ themes), resulting in five R01 FOAs and five R21 FOAs.

Like the second set, these updated PQs also represent diverse fields relevant to cancer research, but all are framed to inspire interested scientists to conceive new approaches and/or feasible solutions. These PQs are not intended to represent the full range of NCI's priorities in cancer research. Rather, they are meant to challenge cancer researchers to think about and elucidate specific problems in key areas of cancer research that are deemed important but have not received sufficient attention.

The Nature of Scientific Problems Underlying PQs

Regardless of topical area, most scientific problems underlying the corresponding PQs fall into one of three broad types:

• Ignored or neglected cancer-relevant problems that are brought back into focus.  These problems typically relate to intriguing older observations or unresolved issues, for which satisfactory, rigorous research answers may open up qualitatively new research avenues and/or result in substantial progress in a given area.
• More recent findings that are perplexing or paradoxical, revealing important gaps in current knowledge. Research answers to these problems are expected to have exceptionally high potential to re-shape current key conception and paradigms about cancer. 
• Problems of recognized high importance that used to be particularly difficult to explore but became open to investigations because of recent scientific discoveries and technical advances.

Each application must address one and only one specific PQ from Group B, exactly as defined in this FOA.

PQB1: (Retained from 2012) Why do second, independent cancers occur at higher rates in patients who have survived a primary cancer than in a cancer-na ve population?

PQB2: (Rewritten for 2013) What molecular and cellular events in the tumor microenvironment (for example, the local immune response) determine if a tumor at the earliest stages of malignant transformation is eliminated, stimulated for further development, or made indolent?

PQB3: (Rewritten for 2013) What mechanisms initiate or sustain cancer cachexia, and can we target them to extend lifespan and quality of life for cancer patients?

PQB4: (New for 2013) What methods can be devised to characterize the functional state of individual cells within a solid tumor?

Specific Requirements

Scientific Scope. The collective scientific scope of this FOA is defined by the list of PQs in Group B. These PQs define research areas appropriate for this FOA. They should NOT be construed as examples of specific topics. The scientific scope of each individual application must clearly and distinctly correspond to one (and only one) of the PQs listed above. Within an area defined by a given PQ, applicants may propose and pursue any topic they deem relevant as a "research answer" to that PQ. It is important, however, that applicants visit the Provocative Questions web site (http://provocativequestions.nci.nih.gov/) for additional information for each PQ pertaining to context, background, feasibility, and expectations of needs to be accomplished for a successful solving of these problems. 

Applicants who fail to choose a specific PQ from this list, address more than one PQ within a single application, and/or re-write the PQ will have their applications assessed as non-responsive. Non-responsive applications will not be reviewed.

Applicants wishing to address more than one of the PQs may still do so by submitting separate applications.

Individual Goals. Within the research area defined by a specific PQ chosen, the overarching goal of the proposed research project must be an attempt to provide definitive, comprehensive, and thorough research answers to the problem or portions of the problem presented by that question. The proposed research solutions are expected to be creative and highly original with a high potential for transformative impact on current concepts and paradigms in cancer research.

Within this general requirement, specific topics for the proposed investigations, strategies, priority directions, and other details of study design and execution are left to the discretion, originality, and creativity of the applicants. The creativity and originality (combined with scientific rigor) are particularly important, given that the areas identified by the individual PQs are, generally, understudied. Therefore, the applicants have the full freedom to identify the most promising direction(s) to address the selected PQ, formulate Specific Aims, choose optimal experimental approaches, and adapt appropriate specific benchmarks as measures of accomplishing the overarching goal of the project. It is important that these specific benchmarks will be in line with Implications of Success identified for each of the PQs on the Provocative Questions website (http://provocativequestions.nci.nih.gov/).

Original Rigorous Concepts versus Preliminary Data. In general, the R21 funding mechanism is used for pilot, exploratory research projects. For such projects, preliminary data are not required, although may be included if available. It is realized that for the areas of the PQs, there could be gaps in background information and original preliminary data may be particularly scarce or hard to get beforehand. The intention of this FOA is, by definition, to exploit understudied areas. Therefore, the emphasis of this R21 FOA is on concepts to be explored, i.e. the power of ideas behind the proposed research. These concepts and ideas must be original but also rigorous in terms of integrating to the best extent possible the available incomplete information for a given area from various sources. These requirements are similar to those for the companion R01 FOA (RFA-CA-13-018), except that the scope of R21 projects is expected be narrower and in some cases the projects may be based on more speculative, high-risk concepts.

Required for Responsiveness

All applications submitted in response to this FOA are expected to pose an original high impact hypothesis (that may be risky) but also a solid research plan to validate the assumptions and test the hypothesis.

Therefore, all applications must contain a Challenge Statement (to be included under Research Strategy Section, see Section IV. Application and Submission Information of this FOA for details). Applications without a Challenge Statement will be considered non-responsive.  Non responsive applications will not be reviewed. The Challenge Statement must convincingly address the following aspects:

• Original Hypothesis;
• Transformative Potential;
• Innovative Approach;
• Testable Conceptual Assumptions; and
• Benchmarks for Hypothesis Validation.

All application titles must begin with the PQ number on which the application is based (insert PQ number at the beginning of the title in parenthesis).

Not Responsive

The following types of projects are not appropriate for this FOA and applications proposing such projects will not be reviewed:

• Applications that fail to provide specific, convincing, and properly organized/structured information (see above) that reviewers can use to assess whether the proposed project truly goes beyond widely accepted concepts, uses novel approaches, and promises substantially more significant outcomes than incremental expansion of the current knowledge.

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 The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. For the group of PQs covered by this FOA (Group B), the NCI intends to fund approximately three R21 awards per due date, corresponding to a total of up to $0.5-1 million, for the first submission round (2014) and a similar amount for the second (2015). Future year amounts will depend on annual appropriations.
Award Budget	The combined budget for direct costs for the two year project period may not exceed $275,000. No more than $200,000 may be requested in any single year. Application budgets must reflect the actual needs of the proposed project.
Award Project Period	The total project period may not exceed 2 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 research - include the PQ number being addressed at the beginning of the title (in parenthesis);

• 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:

Emily J. Greenspan, Ph.D.
Center for Strategic Scientific Initiatives
Office of the Director
National Cancer Institute
31 Center Drive, Room 10A33
Bethesda, MD 20892
Telephone: 301-496-1045
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

Descriptive Title of Applicant’s Project: All application titles must begin with the PQ number on which the application is based (insert PQ number at the beginning of the title in parenthesis).

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: This section must address the expected overall impact of the project outcomes in terms of breadth and magnitude on cancer research.

Research Strategy: This section must contain the following elements:

Research Strategy: this section must contain (place at the beginning of the section and within the standard page limits) the following elements:

• Provocative Question (PQ) Choice. Identify one (and only one) specific PQ from Group B that is being addressed in the proposed project and briefly describe how you propose to provide an answer to the PQ selected.
• Challenge Statement. The Challenge Statement must address briefly (up to 1 page or less) the following:
  • Original Hypothesis. Clearly state the hypothesis addressing the selected PQ.
  • Transformative Potential. Justify why the stated hypothesis would be transformative if validated. Why is testing the proposed concept/hypothesis and/or solving the problem important for the field defined by that particular PQ?
  • Innovative Approaches. Comparing to similar studies, explain why the proposed hypothesis and/or approach are radically different and innovative. What aspects make the proposed approach novel, different, and/or better from previous attempts?
  • Testable Conceptual Assumptions. State specific, testable assumptions that underlie the stated hypothesis; and
  • Benchmarks for Hypothesis Validation. What will be the main, rigorous measures to test the assumptions and then demonstrate the validity of the hypothesis?

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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, NIH and for responsiveness by the National Cancer Institute, NIH. Applications that are incomplete and/or non-responsive 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:

It is essential that research projects proposed in response to this FOA meet the expectations in terms of exceptional creativity and originality in addressing the selected PQ. To be viewed as having potential high impact, the proposed research projects, as designed, must be likely to yield far- or broad-reaching advances in the understanding of the research problem defined by the selected PQ. Thus, potential impact of the applications will be judged in large part on the power of the ideas behind the proposed research.

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. A 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.

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?

Specific to this FOA: How convincing and strong are arguments (including those summarized in the Challenge Statement) that the proposed research project will have profoundly more significant outcomes than incremental expansion of the current knowledge? To what extent is this research project, as designed, likely to yield far- or broad-reaching advances in our understanding for the selected PQ?

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?

Specific to this FOA: Does the proposed project address the selected PQ in a new and fresh way? Does it provide opportunity for novel findings that would be informative as answers for the selected PQ? For high risk projects, is the potential for benefit justifiably high? In cases where the proposed project is an extension of ongoing work, does it address truly original concepts and/or research directions not covered by the ongoing work in a creative, innovative way rather than simply taking the next logical step?

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 clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: Is the experimental design optimal to ensure generation of important information for the selected PQ? If negative results are obtained, how likely is it that these results will be informative for our understanding of the selected PQ? Do the applicants propose a conceptually original and rigorous strategy to solve the problem defined by the selected PQ?

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?

Specific to this FOA: Are there any extraordinary aspects and/or resources that provide novel or enhanced opportunities to investigate the selected PQ in a way that would not be possible elsewhere even in generally excellent scientific environments? For example, are there any unique, newly developed/acquired technical capabilities (without which the project could not be proposed) that are not available anywhere else?

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.

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 clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the 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:

• Will undergo a selection process in which only those applications deemed to have the highest scientific and technical merit will be discussed and assigned an overall impact/priority 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 NCI. 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 Center Telephone: 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]

Emily J. Greenspan, Ph.D.
Office of the Director
National Cancer Institute
Telephone: 301-496-1045
Email: [email protected]

Referral Officer
Division of Extramural Activities
National Cancer Institute
Telephone: 240-276-6390
Email: [email protected]

Crystal Wolfrey
Office of Grants Administration
National Cancer Institute
Telephone: 240-276-6277
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.