National Institutes of Health (NIH)
National Cancer Institute (NCI)
Funding Opportunity Title
Early Phase Clinical Trials in Imaging and Image-Guided Interventions (R21)
R21 Exploratory/Developmental Research Grant Award
Funding Opportunity Announcement (FOA) Number
Catalog of Federal Domestic
Assistance (CFDA) Number(s)
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, and 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. 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 Center and/or Cooperative Groups.
May 24, 2011
Open Date (Earliest Submission Date)
June 27, 2011
Letter of Intent Due Date
Application Due Date(s)
July 27, 2011; November 10, 2011; March 13, 2012; July 11, 2012; November 13, 2012; March 13, 2013; July 11, 2013; November 13, 2013; March 13, 2014, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)
Scientific Merit Review
October/November 2011; February/March 2012; June/July 2012; October/November 2012; February/March 2013; June/July 2013; October/November 2013; February/March 2014; June/July 2014
Advisory Council Review
January 2012; May 2012; October 2012; January 2013; May 2013; October 2013; January 2014; May 2014; October 2014
Earliest Start Date(s)
April 2012; July 2012; December 2012; April 2013; July 2013; December 2013; April 2014; July 2014; December 2014
(Now Expired February 20, 2014 per issuance of PAR-14-013), Originally March 14, 2014
Due Dates for E.O. 12372
Required Application Instructions
It is critical that applicants follow the instructions in the SF 424 (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 primary focus of this FOA is to promote the conduct of early phase clinical trials for: preliminary clinical evaluation of the safety and efficacy of imaging agents; assessment of imaging and IGI systems and methods; contrast kinetic modeling; quantitative tools in imaging; and image-guided drug delivery. This FOA builds upon the success of its predecessor FOA, PAR-08-147 entitled " Quick-Trials for Imaging and Image-Guided Interventions: Exploratory Grants (R21)". Through this FOA, funding is primarily provided for early phase clinical trials that are designed and developed in such a way as to facilitate completion within 2 years.
Imaging is a vital tool in all aspects of the clinical management of cancer including screening, diagnosis, interventions, and monitoring of responses to therapy and surveillance. Great strides have been made in the understanding of the biology and pathophysiology of cancer due to the advent of sophisticated imaging techniques.
There has been a significant investment of resources by the NCI in imaging, for both the understanding of cancer biology and the improvement of the clinical management of cancer patients. This investment has stimulated considerable additional research activity in the fields of new imaging devices, imaging agent development, and image-guided intervention (IGI), systems, methodologies, and therapies. Consequently, there are now many new approaches in cancer imaging and IGI at the preclinical stage of development. As agents, modalities and methodologies go through preclinical evaluations with promising results, they need to be further developed, utilized, and subsequently validated in clinical settings to allow for better tumor diagnosis, staging, intervention, and monitoring of response to therapy in both the general population and underserved populations. For instance, functional imaging methods that would provide clinicians with a better understanding of the effects of a given treatment, at time-points early enough to impact treatment selection and overall management, will allow treatments to be tailored to the individual patient. 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. Early clinical trials of novel imaging agents and methodologies are needed to establish their safety and efficacy, as well as to advance scientific understanding of their clinical potentials. In addition, in many cases incorporation of advanced imaging and IGI techniques into clinical trials remains difficult, not in-pace with clinical need, and under supported. Hence, there is a critical need for a funding initiative for early phase trials which helps accelerate 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.
This FOA will provide a mechanism by which to accelerate the development of these modalities, methodologies, and agents through the early stages of clinical development. This FOA will provide investigators with support for pilot (Phase I and II) cancer clinical trials, inclusive of patient monitoring and relevant laboratory studies. 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 Cooperative Groups.
Functional imaging and image-guided interventions that will 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.
Features of this program include a modular budget and inclusion of the clinical protocol within the grant application. Inclusion of the complete clinical protocol within the human subjects section of the application is important and will ensure proper peer review of the application. Though not required, a copy of the corresponding Institutional Review Board (IRB) application can be submitted with this application to facilitate completion of the proposed research in the 2-year timeframe. Other key features include no requirement for extensive preliminary data in the application (although applicants must demonstrate that the proposed imaging or IGI solutions are ready for use in human subjects, prior to award), support for exploratory translational research studies, and rapid development and application of novel clinical imaging and IGI in cancer-related applications.
Applications that exclusively address phantom and pre-clinical studies will not be considered appropriate for this FOA.
Application Types Allowed
The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards
All awards are for up to $500,000 in Direct Costs over 2 years. Although the financial plans of the NIH institute(s) and center(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.
Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $500,000 in Direct Costs over a two-year period, with no more than $250,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $500,000 for the combined two-year award period. 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.
1. Eligible Applicants
Higher Education Institutions:
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For profit Organizations
Foreign (non-U.S.) components of U.S. Organizations are allowed.
Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
All Program Directors/Principal Investigators (PD/PIs) must
also work with their institutional officials to register with the eRA Commons
or ensure their existing eRA Commons account is affiliated with the eRA Commons
account of the applicant organization.
Eligible Individuals (Project Director/Principal Investigator)
Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Project Director/Principal
Investigator (PD/PI) 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.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Number of Applications
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide. Applicants may submit a resubmission, but such applications must include an Introduction addressing issues raised in the previous critique (Summary Statement).
Exploratory/developmental grant support is for new projects only; Renewal applications will not be accepted. Applicants may submit more than one application, provided each application is scientifically distinct.
1. Requesting an Application Package
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.
Required and Optional Components
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
PHS 398 Research Plan Component
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
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)
Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.
3. Submission Dates and Times
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via 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.
Applicants are responsible for viewing their application 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.
4. Intergovernmental Review (E.O. 12372)
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.
6. Other Submission Requirements and Information
Applications must be submitted electronically following the instructions described in the SF 424 (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.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.
Inclusion of Clinical Protocols
The SF424 (R&R) Application guide (http://grants.nih.gov/grants/funding/424/index.htm)
specifically states that “Surveys, questionnaires, and other data collection
instruments; clinical protocols and informed consent documents may be submitted
in the Appendix as necessary.” In addition, any information pertaining to
clinical protocols that can be used as part of the initial peer review must be
included in the Research Strategy of the PHS 398 Research Plan component.
Note: For each clinical trial 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.
Although NIH does not require certification of IRB approval of the proposed research prior to NIH peer review of an application, to ensure timely commencement of the research, investigators are encouraged to initiate planning the IRB review process so that certification of IRB approval can be requested as Just-in-time (JIT) information prior to award. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-031.html.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
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/priority 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).
Scored Review Criteria
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.
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?
Are the PD/PIs, 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?
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? Is an existing concept, methodology, instrumentation, or intervention being applied in a novel way?
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?
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
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 completions in a 2-year timeframe? Is the proposed clinical trial protocol congruent with the overall goals of the proposal?
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?
Additional Review Criteria
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/priority 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.
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 Human Subjects Protection and Inclusion Guidelines.
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.
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.
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.
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.
Additional Review Considerations
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/priority 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.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.
As part of the scientific peer review, all applications:
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 Board. The following will be considered in making funding decisions:
3. Anticipated Announcement and Award Dates
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.
1. Award Notices
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
2. Administrative and National Policy Requirements
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
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually 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.
Application Submission Contacts
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
eRA Commons Help Desk(Questions regarding eRA Commons
registration, tracking application status, post submission issues)
(For Imaging trials)
Lori A. Henderson, Ph.D.
Frank I. Lin, M.D.
(For Image-Guided Intervention [IGI] trials)
Keyvan Farahani, Ph.D.
(For Radiation Therapy related trials)
Bhadrasain Vikram, M.D.
Peer Review Contact(s)
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Financial/Grants Management Contact(s)
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.
Authority and Regulations
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.