Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	Early Phase Clinical Trials in Imaging and Image-Guided Interventions (R21)
Activity Code	R21 Exploratory/Developmental Research Grant
Announcement Type	Reissue of PAR-11-216
Related Notices	March 28, 2014 - See Notice NOT-CA-14-036. Notice of Expiration of this PAR, immediately.
Funding Opportunity Announcement (FOA) Number	PAR-14-013
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.394, 93.395
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) is intended to support clinical trials conducting preliminary evaluation of the safety and efficacy of imaging agents, as well as an assessment of imaging systems, image processing, image-guided therapy, contrast kinetic modeling, 3-D reconstruction and other quantitative tools. As many such preliminary evaluations are early in development, this FOA will provide investigators with support for pilot (Phase I and II) cancer imaging clinical trials, including patient monitoring and laboratory studies. This FOA supports novel uses of known/standard clinical imaging agents and methods as well as the evaluation of new agents, systems, or methods. The imaging and image-guided intervention (IGI) investigations, if proven successful in these early clinical trials, can then be validated in larger studies through competitive R01 mechanisms, or through clinical trials in the Specialized Programs of Research Excellence (SPOREs), Cancer Centers and/or the NCI's National Clinical Trials Network.

Posted Date	February 19, 2014
Open Date (Earliest Submission Date)	May 30, 2014
Letter of Intent Due Date(s)	30 days before the application due date
Application Due Date(s)	June 30, 2014; October 10, 2014; February 9, 2015, June 9, 2015; October 9, 2015; February 9, 2015; June 9, 2016; October 11, 2016; February 9, 2017, 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	October/November 2014; February/March 2015; June/July 2015; October/November 2015; February/March 2016; June/July 2016; October/November 2016; February/March 2017; June/July 2017
Advisory Council Review	January 2015; May 2015; October 2015; January 2016; May 2016; October 2016; January 2017; May 2017; October 2017
Earliest Start Date	April 2015; July 2015; December 2015; April 2016; July 2016; December 2016; April 2017; July 2017; December 2017
Expiration Date	(Now Expired March 29, 2014 per NOT-CA-14-036), Originally February 10, 2017
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) is intended to support clinical trials conducting preliminary evaluation of the safety and efficacy of imaging agents, as well as an assessment of imaging systems, image processing, image-guided therapy, contrast kinetic modeling, 3-D reconstruction and other quantitative tools. As many such preliminary evaluations are early in development, this FOA will provide investigators with support for pilot (Phase I and II) cancer imaging clinical trials, including patient monitoring and laboratory studies. This FOA supports novel uses of known/standard clinical imaging agents and methods as well as the evaluation of new agents, systems, or methods. The imaging and image-guided intervention (IGI) investigations, if proven successful in these early clinical trials, can then be validated in larger studies through competitive R01 mechanisms, or through clinical trials in the Specialized Programs of Research Excellence (SPOREs), Cancer Centers and/or the NCI's National Clinical Trials Network.

Imaging performs vital roles in all aspects of clinical management of cancer including screening, diagnosis, interventions, monitoring of therapeutic response, and surveillance. The advent of effective imaging techniques has enabled great strides in understanding the biology and pathophysiology of cancer.

NCI has invested significant resources in imaging, both to understand cancer biology and to improve clinical management of cancer patients. This investment has stimulated considerable research activity in the fields of new imaging devices, imaging agent development, and image-guided intervention (IGI), systems, methodologies, and therapies. For example, investigators are developing interleukin-2 radiopharmaceuticals known to detect organ infiltrating T cells in human autoimmune diseases, a new PET imaging diagnostic assay to evaluate how well Sarcoma/Abelson tyrosine kinase inhibitors target tumors inside patients, and leveraging sophisticated computer vision, image analysis, computer assisted diagnostic and deformable registration tools to improve the delineation of tumors for targeted laser ablation therapy via multi-parametric MRI. In addition, researchers are also focused on novel uses of clinical imaging technologies to meet the needs of medical oncologists. Molecular and functional imaging methods, for instance, are being investigated to provide clinicians with a better understanding of the effects of a given treatment and at time-points early enough to impact treatment selection and overall management. This early understanding of the effects of a given therapy or intervention could potentially allow clinicians to switch to more effective treatments saving patients from untoward side effects or death, saving both lives and resources. Today, there are many new approaches in cancer imaging and IGI at the preclinical stage of development that need to be optimized and validated in a clinical setting to determine their impact upon tumor diagnosis, staging, intervention, therapeutic response monitoring, and surveillance. These preliminary clinical studies would serve a number of societal interests in improved cancer care in the general population as well as better serving underserved populations.

Despite these discoveries and opportunities, the incorporation of advanced imaging and IGI techniques into clinical trials remains difficult, not in-pace with clinical need, and under supported. Therefore, the purpose of this initiative is to promote the use of advanced imaging and provide the necessary support for the assessment of imaging modalities, methodologies, and agents as well as IGI methods through the early stages of clinical evaluation in both the general and underserved populations.

The goal of this FOA is to promote and accelerate clinical evaluation of imaging modalities, agents, methods, and image-guided interventions to improve cancer management. Therefore, projects that propose Phase I or early Phase II studies of imaging agents and methodologies, or feasibility studies of imaging devices, image-guided surgery or therapies, image-guided radiation therapy using external beams and/or systemic radionuclides, should show that the anticipated preliminary data will be able to justify a future grant application for confirmatory Phase II or Phase III trial. A range of trials at different stages of development are allowed, including first in human Phase I and II single-site or multi-site studies based on conventional or adaptive trial designs (if economically feasible). The early studies should provide important initial information regarding imaging investigations (e.g. safety, tolerability, dosing). Later-stage studies should yield data that allow clear go/no-go decisions regarding whether these imaging investigations or image-guided interventions should proceed to an efficacy trial. Applicants may, for example, propose to conduct a clinical trial where the primary aim is to:

• Evaluate and optimize the dose, safety, tolerability or pharmacokinetics of an imaging agent or intervention in a target population.
• Produce sufficient evidence of short-term activity (e.g., imaging biomarker activity, pharmacodynamic response, target engagement, dose-response trends) in a human proof of concept trial.
• Select or rank the best of two or more potential imaging interventions, technologies, or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., a futility trial.)
• Conduct exploratory IND studies with less preclinical toxicity data or less micro-dosing of investigational agents than usually required for traditional first in human studies to improve the trial design and efficiency in subsequent trials. See FDA's website for information regarding FDA's Exploratory IND Guidance document.

If proven successful, these investigations can then be validated in larger studies through competitive R01 mechanisms, or through clinical trials in the Specialized Programs of Research Excellence (SPOREs), Cancer Centers, and/or the NCI’s National Clinical Trials Network program.

This FOA is applicable to a broad range of clinical imaging evaluations associated with or without therapeutic endpoints. For example, the testing of imaging biomarkers can be in the context of distinguishing aggressive from indolent tumors/disease or selecting appropriate risk adaptive therapies (e.g., image-guided radiation therapy using external beams and/or systemic radionuclides) or risk stratification. Projects in any area of technology development that advance cancer-related imaging science through clinical trials are welcome provided sufficient pre-clinical evidence has been established to validate use in clinical studies. Examples of appropriate scientific interests under this FOA include, but are not limited to the assessment of: imaging agents and imaging assays (biodistributions, pharmacokinetics, tracer kinetic modeling, etc.), imaging systems and devices (advances in multi-modality instrumentation, etc.), advanced image processing and analysis techniques to improve cancer care. Opportunities where the proposed imaging agents and technologies can be explored in the context of NCI's high priority targets in cancer research (e.g. signaling pathways, tumor biology, etc.) or linked to developments stemming from NCI's current activities (e.g. Cancer Therapeutic Evaluation Program's Phase II consortia, Cancer Imaging Program's Quantitative Imaging Network, NCI's Experimental Therapeutics program (NeXT)) are also encouraged.

Molecular and functional imaging, as well as image-guided interventions that help address health issues and disparities in underserved populations, will also be considered for this FOA. Examples of issues that can be examined include, but are not limited to, novel imaging or image-guided approaches to evaluate differences in safety and efficacy of imaging agents and monitoring of differences in response to therapy among different racial and ethnic populations.

Key features of this FOA are consistent with the standard R21 mechanism in which prospective clinical trials are proposed where: extensive preliminary data are not required, high risk novel clinical imaging and IGI investigations are feasible, and the studies are supported by a 2 year modular budget. This FOA supports exploratory and developmental research projects in which prospective clinical trials are proposed where high risk novel clinical imaging and IGI investigations are feasible. Extensive preliminary data are not required.

Applications submitted under this FOA should address the following requirements to ensure proper peer review and better assure completion of the proposed clinical trial in 2 years.

• First, a full and complete clinical protocol must be included in the SF424(R&R) Other Project Information.
• Second, applicants must demonstrate that the proposed imaging or IGI solutions are ready for use in human subjects in their application. . This means that pre-clinical safety and tolerability must be established before one can apply.
• Third, applicants are encouraged to apply for an Investigational New Drug (IND) approval or Investigational Device Exemption (IDE), as necessary, prior to or at the time of submission to show that the proposed trial can start promptly upon award.

Applicants are also reminded that an award cannot be made without providing NIH documentation of IRB approval of the human subjects protocols. Although the NIH policy does not require this approval at the time of submission, the institution may still determine that certain lines of research (e.g., scientifically or ethically controversial research) or mechanisms of research (e.g., multicenter clinical trials) should receive IRB review prior to submission of the application. Otherwise, applicants should strongly consider proceeding with IRB review immediately following Scientific Peer Review. See NIH IRB policy for details (http://grants.nih.gov/grants/policy/hs/).

This FOA is not intended to support applications or research projects that:

• Propose any pre-clinical animal studies.
• Address phantom studies beyond their use for imaging quality assurance.
• Study human tissue samples without otherwise involving human subjects in an appropriate imaging clinical trial.
• Focus on the retrospective analyses of images and image data alone. Only prospective clinical trials will be supported by this FOA in accordance with the NIH definition of a clinical trial which states: "A prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective."

Researchers uncertain as to whether their intended technology development project meets the overall requirements of this FOA are encouraged to contact the appropriate NCI official listed in the Scientific/Research Contact section of this FOA (see Section VII. Agency Contacts.

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 Revision 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.
Award Budget	The combined budget for direct costs for the 2-year project period may not exceed $275,000. No more than $200,000 may be requested in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined 2-year award period.
Award Project Period	The total project period for an application submitted in response to this funding opportunity 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 to assess responsiveness and 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:

Lori Henderson, Ph.D.
Clinical Trials Branch
Cancer Imaging Program
National Cancer Institute
9609 Medical Center Drive
Bethesda, MD 20892
Telephone: 240-276-5930
Fax: 240-276-7890
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 with the following additional instructions:

Other Attachments

Clinical Trials Protocol: Because the merit of the proposed study will be documented by the attached clinical trials protocol(s) include the full documentation for the Clinical Trials Protocol, on which the proposed studies are based. Collate all documents in one file (with the list of documents at the beginning). Use filename "Clinical Trials Protocol". (Note that this filename will become a bookmark in the application.) If more than one Clinical Trial Protocol is included, it should be submitted as a separate Other Attachment with a unique identifier added to the filename, e.g., Clinical Trials Protocol 2.

More than one clinical trials protocol may be submitted to this FOA, provided it meets the research objectives of this FOA and time/budget constraints. For each Clinical Trials Protocol included, please specify if it is: (1) based on an active, ongoing clinical trial that has been (or will be) amended to include the research study proposed in the R21 application; or (2) a newly designed clinical protocol that is currently undergoing Institutional Review Board (IRB) review.

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.

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, NIH. Applications that are incomplete 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 to this FOA: Have the proposed tools and technologies been sufficiently developed at a preclinical stage to warrant further evaluation in an early phase clinical trial?

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 to this FOA: Since innovation - as defined in this PAR's context - includes investigations of novel or advanced imaging and/or IGI methods in early phase clinical trials, will the proposed research seek to challenge existing paradigms or offer the possibility of new methods for diagnosis, intervention, and response evaluation of targeted cancer problems?

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? In addition, specific to this FOA: While the proposed study can be a small pilot/feasibility study for which extensive preliminary human data may not be necessary, is the proposed research supported by enough basic science or preliminary work in animal models to be ready for further evaluation as an early phase clinical trial? Is the proposed research designed and developed in such a way as to facilitate completion in a 2-year timeframe? Is the proposed clinical trial protocol congruent with the overall goals of the application?

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.

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

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Council or 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]

For Imaging trials:

Lori A. Henderson, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5930
E-mail: [email protected]

Frank I. Lin, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-5932
E-mail: [email protected]

For Image-Guided Intervention [IGI] trials:

Keyvan Farahani, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5921
E-mail: [email protected]

For Radiation Therapy related trials:

Bhadrasain Vikram, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-5690
E-mail: [email protected]

Eileen Bradley, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1179
E-mail: [email protected]

Barbara A. Fisher
National Cancer Institute (NCI)
Telephone: 301 631-3012
E-mail: [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.