Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Cancer Institute (NCI), (http://www.cancer.gov)

Title: Academic-Industrial Partnerships for Translation of in vivo Imaging Systems for Cancer Investigations (R01)

Announcement Type
This Funding Opportunity Announcement (FOA) is a reissue of PAR-07-214

Update: The following updates relating to this announcement have been issued:

• April 5, 2013 - This PAR has been expired and reissued as PAR-13-169.
• April 19, 2011 - See Notice NOT-CA-11-011 The purpose of this Notice is to clarify specific issues pertinent to the scientific scope and requirements of PAR-11-150.
• September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011. Adobe B1 forms are required for due dates on or after May 8, 2011.
• August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

Program Announcement (PA) Number: PAR-10-169

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.394, 93.395, 93.396

Key Dates
Release/Posted Date: April 16, 2010
Opening Date: May 5, 2010 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not Applicable
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: (Now Expired April 05, 2013 per issuance of PAR-13-169), Originally May 8, 2013

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. This Funding Opportunity Announcement (FOA) issued by the Cancer Imaging and Radiation Research Programs of the National Cancer Institute (NCI), National Institutes of Health (NIH), encourages applications from research partnerships formed by academic and industrial investigators to accelerate the translation of either animal or human in vivo imaging, image guided, and/or spectroscopic systems and methods designed to solve targeted cancer problems for cancer research, clinical trials, and/or clinical practice. The partners on each application will establish an inter-disciplinary, multi-institutional research team to work in a strategic alliance to implement a coherent strategy to develop and translate the proposed system or methods with potential for significant impact on preclinical, single, or multisite clinical studies. Partnerships must include at least one lead academic and one lead industrial organization large or small among their numbers. For either preclinical or clinical research, funding may be requested for limited additional copies of prototype systems and methods in order to optimize and validate them across different platforms and/or research sites. Each partnership is encouraged to plan to solve its choice of targeted cancer problem within the five year funding period. This FOA supports clinical trials that emphasize optimization and validation of the performance of imaging systems, including devices, agents and/or methods. It will not support commercial production.
• Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism.
• Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
• Budget and Project Period. The total project period for an application submitted in response to this funding opportunity may not exceed 5 years. Applicants for an R01 award are not limited in dollars but need to reflect the actual needs of the proposed project.
• Application Research Strategy Length: The R01 application Research Strategy section of the PHS398 may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts. See Table of Page Limits.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.
• Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.
• Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).
• Renewals. Applicants may submit a renewal application.
• Application Materials. See Section IV.1 for application materials.
  General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:
  • SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
  • General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review, and Anticipated Start Dates
1. Letter of Intent
B. Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

This Funding Opportunity Announcement (FOA) issued by the Cancer Imaging and Radiation Research Programs of the National Cancer Institute (NCI), National Institutes of Health (NIH), encourages applications from research partnerships formed by academic and industrial investigators to accelerate the translation of either animal or human in vivo imaging, image guided, and/or spectroscopic systems and methods designed to solve targeted cancer problems for cancer research, clinical trials, and/or clinical practice. The partners on each application will establish an inter-disciplinary, multi-institutional research team to work in a strategic alliance to implement a coherent strategy to develop and translate the proposed system or methods with potential for significant impact on preclinical, single, or multisite clinical studies. Partnerships must include at least one lead academic and one lead industrial organization large or small among their numbers. For either preclinical or clinical research, funding may be requested for limited additional copies of prototype systems and methods in order to optimize and validate them across different platforms and/or research sites. Each partnership is encouraged to plan to solve its choice of targeted cancer problem within the five year funding period. This FOA supports clinical trials that emphasize optimization and validation of the performance of imaging systems, including devices, agents and/or methods. It will not support commercial production.

Background

A. Translational Research

The Translational Research Working Group (TRWG) was established in the summer of 2005 to conduct a discussion with the broader cancer research community and develop recommendations about how the National Cancer Institute (NCI) can best organize its investment to further "translational research .

The TRWG reached an operational definition of translational research: Research that transforms scientific discoveries arising in the lab, clinic, or population into new clinical tools and applications that reduce cancer incidence, morbidity, and mortality . The TRWG did not seek to change any aspect of discovery research, which is the largest component of the NCI extramural research funding portfolio (See http://www.cancer.gov/trwg/TRWG-definition-and-TR-continuum).

The TRWG recognized from its onset that the NCI-supported translational research enterprise was not keeping pace with the enormous opportunities presented by advances in knowledge and technology over the past 40 years of cancer research. In a 2007 report (http://www.cancer.gov/aboutnci/trwg/Order-final-report) the TRWG recognized the need for specific programmatic focus on collaborative early translational research projects that integrate the complementary skills and expertise of both academic institutions and pharmaceutical and biotechnology companies to jointly pursue specific early-stage product development opportunities. The 2007 TRWG Report reflects the fact that translational research is a central, major interest of NCI leadership and advisory boards.

For this FOA, translational research must be goal oriented and designed to meet performance requirements to solve a targeted cancer problem in either preclinical and/or clinical settings. Innovation for this FOA is a coherent plan to deliver robust new capabilities for preclinical or clinical use. Scientific innovation alone is neither the main thrust nor sufficient because innovation is complete only when delivered as new capabilities to end users, i.e., it is innovative to finish and deliver something new. Further clarification of translational research emphasis is provided in the following sections for both current and next generation of imaging platforms and methods.

B. Current Clinical Imaging Platforms

Recent advances in the development of anatomical, functional, and molecular imaging methods are having significant impact on preclinical (animal) and clinical cancer research for early cancer detection, screening, diagnosis, prediction of response, measurement of response to therapy, and image-guided intervention or drug delivery systems. For the current generation of commercial imaging platforms, there is a need to develop, optimize, and validate imaging protocols and data analysis methods. For example, these may include methods to improve data collection, modeling, and analysis that are specifically optimized and validated for a targeted cancer problem. This is particularly important in the new era of personalized medicine and the role of imaging for patient stratification and measurement of response to therapy, i.e., as required for adaptive clinical trial strategies for drug or radiation therapy. Alternatively, translational research may address the development and characterization of imaging probes or agents that will be implemented on current commercial imaging platforms. These methods do not necessarily need to be highly innovative from a technology development perspective, and may include simple procedures applied to anatomical imaging, as well as more complex functional and molecular imaging methods. The overriding factor is the need for strategies to optimize, validate, and otherwise meet the robust performance requirements necessary to deliver the innovation as new capabilities for either multi-platform and/or multi-site preclinical or clinical investigations.

Next-Generation Clinical Imaging Platforms: The development, optimization, and validation of next-generation imaging technologies and methods for targeted cancer investigations can be complex and pose additional translational research problems. For example, there is a recent trend toward quantitative multimodal imaging in which the physical characteristics of one imaging system are used to improve the quantitative performance of another system. Multimodal imaging platforms such as CT and PET, CT and SPECT, MRI and PET, or MRI and Optical are being explored for their ability to encompass anatomical, functional, and molecular imaging methods. The use of single or multiple contrast agents or nano-carriers developed for one or more imaging systems for purposes that include transport of therapeutic agents, adds complexity to their design, optimization and validation. Thus, translational strategies may be much more complex than the underlying technology development, and require innovative translational research solutions to deliver new capabilities. Applications that use endogenous contrast and/or FDA-approved agents avoid extra steps of translational complexity.

Preclinical Imaging Platforms: Advances in imaging methods for preclinical research provide ways to observe altered pathways, disease progression, and therapeutic response in preclinical models of human disease. Preclinical knowledge gained from animal studies can inform acceptable approaches to translate it to clinical investigations. Recent progress in genomics and proteomics, studies of cell-cycle pathways, and molecular imaging are advancing our knowledge of the molecular basis of tumor biology. Preclinical imaging technology platforms and methods face many of the same developmental and translation challenges as those for human investigations. For this FOA the innovation in translational research for preclinical imaging includes delivery of new and robust performance for preclinical investigations, the results of which can provide benefits for human investigations.

C. Physical and Clinical Validation Strategies

The translational research scope for preclinical or clinical investigations often requires implementation of quantity control (Q/C) and quality assurance (Q/A) methods for the proposed imaging tools. The nature and importance of these methods will vary depending on the proposed preclinical or clinical studies, and in particular, whether longitudinal studies are required. There are needs to assess and verify physical performance, e.g., instrument signal-to-noise, and spatial or temporal resolution. These methods are often not considered scientifically innovative from a technology development perspective, but provide new reliability essential for translational research success.

Translational research studies benefit from correlations with other clinical findings such as pathology, serial biopsies, or preclinical imaging findings, particularly for molecular imaging. Correlative studies with other molecular laboratory methods, including molecular based assays, are supported by this FOA. Validation studies are critically important for the implementation of new capabilities for clinical decision making within the context of personalized medicine or personalized and adaptive drug therapy strategies.

D. Opportunities for Academic-Industrial Partnerships

A prerequisite for participation in this initiative is the formation of an appropriate multi-disciplinary team that includes both academic and industrial scientists. These teams are expected to combine strengths unique to each group to accelerate the translational research goals as defined in this FOA. This prescription is well supported by extensive management science, business administration, and science and technology policy literature that shows that high technology businesses (including those in medical technology) who engage in strategic alliances to accomplish their R&D have greater success rates and higher economic returns than those that work separately.

Academic investigators often focus on the phases of early discovery and invention with priorities set on proof of principle studies, feasibility demonstration, and publication of their findings. They often do not place emphasis on the creative processes involved in the R&D tasks of robust system engineering, validation and translation studies that lead to acceptance and broad application by end-users. Thus, one of the goals of the FOA is to provide support for academic scientists to more actively participate in translational research.

Industrial researchers also encounter barriers that discourage translation of an invention into practice and its delivery to end-users. They must evaluate the expense of developing a new imaging device or method within the larger context of return-on-investment before they commit a company to a new research project. Industry often finds it more cost-effective to license or purchase intellectual property rights from academia, rather than to engage in the discovery and early translational research. Unlike the academic environment, medically oriented industrial research facilities are typically well suited for product R&D and for ensuring compliance with Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP) standards and strict International Standards Organization (ISO) requirements, all necessary for approval of their products by regulatory bodies and also important to meet the translational research goal of delivery of new capabilities to user communities.

Commercial entities tend to avoid risks associated with initiating development of emerging imaging methods with more than a modest level of complexity. For example, industrial endeavors often tend to put priority on modifications to existing imaging products that expand the utility of the imaging platform rather than focus on a targeted cancer problem, where specific claims for FDA approval or CMS reimbursement may be required. A good example is the need for industry-supported clinical decision tools necessary for emerging personalized medicine and therapy treatment strategies.

This FOA is designed to promote new or expanded opportunities for academic-industrial partnerships. The intent is to combine their resources to reduce translational research barriers. Because the dissemination of the proposed imaging systems and methods may require regulatory approval, partnership plans may include travel and support for involvement of NIH Intramural, FDA, and NIST scientists. An important goal of the FOA is to create a multi-disciplinary environment where the academic-industrial partnership will continue to flourish and pursue additional translational research projects.

Specific Research Objectives and Scope of this FOA

Translational imaging research must be goal-oriented and designed to meet the performance requirements for solution of a targeted cancer problem in either preclinical (animal) or clinical cancer arenas. Delivery of innovation, rather than scientific novelty, is the central focus of this FOA. Innovation is the translation and delivery of robust performance of new technological capabilities to end users. Innovation is expected to arise from sound translational effort that delivers new, robust preclinical and clinical capabilities to research and clinical end users.

Respondent academic-industrial partnerships may choose to develop and translate imaging systems, methods, and/or any related component technologies that are designed to address a targeted cancer preclinical or clinical investigation.

If performance in the clinical environment is the chosen end-point, the application should clearly address the project’s significance for potential clinical research or multi-site clinical trial setting. Teams proposing such projects should include physicians as key participants for imaging, oncology, pathology and/or other clinical science as appropriate to a specific research plan. Research plans that reach a level of maturity and validation to support implementation and optimization of multi-site clinical investigations are encouraged. However, large-scale clinical trials or phase 3 trials that correlate findings with clinical outcomes, as opposed to the optimization of imaging methods, are beyond the scope of this FOA and will not be considered appropriate.

The goals of preclinical imaging are to enhance the performance of imaging systems and methods so that they provide robust performance across different platforms or research sites for a targeted cancer problem and permit an efficient transfer of knowledge to human investigations where appropriate. Teams proposing such projects should include imaging physicians, oncologists, molecular and/or preclinical imaging scientists knowledgeable about the targeted applications. However, large-scale basic research projects that do not emphasize translational development and optimization of the methods for a targeted cancer problem will not be considered appropriate to this FOA.

The following list includes some examples of appropriate preclinical and clinical research that address development and validation of imaging platform(s) and method(s) for

• Imaging and/or spectroscopic methods applied to drug discovery, prediction of response, staging of disease, and quantitative measurement of response to drug and/or radiation therapy;
• Minimally-invasive image-guided interventional procedures, including drug or other energy based delivery systems, and related quantitative imaging methods as required for effect, toxicity and/or dosimetry;
• Detection, diagnosis, or screening of precancer or early cancer with improved specificity and sensitivity that permit early intervention by therapy strategies as described above.

Possible technologies and methods designed to address a targeted cancer problem as defined in this FOA include but are not limited to the following:

• Imaging systems or component technologies and related methods that can be incorporated into commercial imaging systems or image-guided interventional or drug delivery platforms;
• Multi-modality imaging systems and methods, including appropriate informatics tools for anatomical, functional, or molecular imaging methods;
• Contrast agents or molecular probes and related nano-carriers;
• Inherent endogenous contrast methods;
• Optimization of imaging systems and methods to accommodate existing approved contrast agents, molecular probes, and/or related nano-carriers; and
• Optimized new image acquisition techniques, image processing and computer-aided detection (CAD) algorithms, data fusion and integration, related informatics technology (IT) tools, and display methods as required for clinical decision making, including their integration into one or more existing or new commercial imaging platforms, where appropriate.

In addition, the research team may engage in the development of research resources and tools during the course of their research program. These could include, for example, methods for image quality control, data collection and analysis for pre clinical or clinical investigations across different commercial imaging platforms and research sites. Specific tools may include, but are not limited to, the following:

• Open source architectures and software tools that can be integrated with commercial imaging systems or implemented on networked computer platforms;
• Web-accessible public resources that permit evaluation of imaging hardware performance, quality assurance, image reconstruction and image normalization methods; and
• Web-accessible public resources that address image annotation, mark-up methods or other methods that may enable comparison of relative performance of different equipment, preprocessing and/or data integration tools.

Support for collaborative activities. In the spirit of strategic alliances to meet the objectives of the partnership program, investigators may include plans to cooperate with one or more NCI-funded centers, networks or consortia, e.g., with U01, U54, U24 awardees, to gain the advantages of broader consensus on translational research methods for validation, qualification, or creation of public research resources for translational research. Support for travel to these research sites may be included. Plans to collaborate with FDA and NIST scientists may also be included, where support for research scientists and travel is permitted.

Specific Research Requirements for this FOA

All applications submitted in response to this FOA are encouraged to conform to the research objectives and requirements of this FOA. Thus, every application should have the following attributes:

• Academic-Industrial Partnership: Co-participation of academic and industrial components is expected from year one of the project. Each application must include a partnership and research plan that reflects an academic-industrial partnership that is either already ongoing or will be active from the beginning of the project. All the partnering institutions will be required to collaborate on the proposed goals in a manner that would enable the entire joint effort to be administered as a single project. Each partner should have sufficient scientific involvement, and at least one participating investigator with qualifications to lead and share authority and responsibility for the project.
• Academic-Industrial Partnership Governance: The application Research Strategy section must include a section on Governance and Organizational Structure that describes the overall organization, major tasks each partner will complete, and benefits each brings to this alliance to enhance prospects for completing specific translational aims. Describe shared leadership, administration, conflict resolution, technical, scientific and preclinical or clinical responsibilities where appropriate.

Related Funding Opportunities

This FOA complements other translational research initiatives of the Cancer Imaging and Radiation Research Programs, such as the following:

• PAR-08-225: Quantitative Imaging for Evaluation of Responses to Cancer Therapies (U01)
• PA-08-147: Quick-Trials for Imaging and Image-Guided Interventions: Exploratory Grants (R21)
• PA-09-253: Image-guided Drug Delivery in Cancer (R01)
• PA-10-079: Image-Guided Cancer Interventions (SBIR [R43/R44])
• PA-10-080: Image-Guided Cancer Interventions (STTR [R41/R42])

Applicants to this FOA are invited to explore affiliation with the Network for Translational Research (NTR; http://imaging.cancer.gov/programsandresources/specializedinitiatives/ntroi) or Quantitative Imaging Network (PAR-08-225), which conduct translational research in imaging.

Investigators seeking to pursue imaging research beyond the scope and requirements of this FOA are referred to the following FOAs:

http://grants.nih.gov/grants/guide/pa-files/PA-10-009.html Bioengineering Research Grants (BRG) [R01]

PA-10-010: Exploratory/Developmental Bioengineering Research Grants (EBRG) [R21]

http://grants.nih.gov/grants/guide/pa-files/PAR-07-352.html Bioengineering Research Partnerships (BRP) [R01]

Researchers who are unclear as to which of the imaging FOAs might be most appropriate for their proposed technology development project are encouraged to contact the program official listed in this FOA.

This FOA supports clinical trials that emphasize optimization and validation of the performance of imaging systems, including devices, agents and/or methods. It will not support commercial production. Large-scale basic research projects that are NOT involved in translational development and optimization of the methods for a targeted cancer problem will not be considered appropriate to this FOA.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This FOA will use the R01 award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) should use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation; see NOT-OD-05-004.

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.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• 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
• 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)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the 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.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and do not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs require additional information, as outlined in the instructions below. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit more than one application, provided that each application is scientifically distinct.

Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and competing renewal applications are permitted only a single amendment (A1). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016). Original new and competing renewal applications that were submitted prior to January 25, 2009 are permitted two amendments (A1 and A2). For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date.

Renewals. Applicants may submit a renewal application.

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

Registration:

Appropriate registrations with Grants.gov and eRA Commons must be completed on or before the due date in order to successfully submit an application. Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered with both Grants.gov and the Commons. All registrations must be complete by the submission deadline for the application to be considered on-time (see 3.C.1 for more information about on-time submission).

A one-time registration is required for institutions/organizations at both:

• Grants.gov (http://www.grants.gov/applicants/get_registered.jsp) and
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered

• Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
• If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  Email [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

• The individual(s) designated as PDs/PIs on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.
• Each PD/PI must hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account.
• When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization. PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons.
• This registration/affiliation must be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PD(s)/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note: The registration process is not sequential. Applicants should begin the registration processes for both Grants.gov and eRA Commons as soon as their organization has obtained a DUNS number. Only one DUNS number is required and the same DUNS number must be referenced when completing Grants.gov registration, eRA Commons registration and the SF424 (R&R) forms.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY: (301) 451-5936

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms for this FOA through Grants.gov/Apply and in accordance with the SF424 (R&R) Application Guide (http://grants.nih.gov/grants/funding/424/index.htm).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application components, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6. regarding appropriate required budget component.)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic [non-U.S.] Entities)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

• Request budgets in U.S. dollars;
• Prepare detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms not the PHS398 Modular Budget component)(see NOT-OD-06-096);
• Not include any charge-back of customs and import fees;
• Comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF;
• If appropriate, request funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) ( see NOT-OD-01-028, March 29, 2001);
• Comply with Federal/NIH policies on human subjects, animals, and biohazards; and
• Comply with Federal/NIH biosafety and biosecurity regulations (see Section VI.2., Administrative and National Policy Requirements )

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Governance and Organizational Structure

All applications must include a section on Governance and Organizational Structure within the Research Strategy section. The leadership team must include the PD/PI of the primary partnering organization and lead co-investigator(s) of the other partnering organization or organizations. Briefly describe the governance and organizational structure of the leadership team and the research project, include communication plans, process for decisions on scientific direction, procedures for resolving conflict, delineate the roles and administrative, technical and scientific responsibilities for the PD/PI, other partners, and collaborators. For Multiple PDs/PIs, describe the rationale for choosing a multiple PDs/PIs approach. If they plan to allocate budgets, delineate the distribution of resources to specific components of the project or the individual PDs/PIs. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered on the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the section of the Research Plan entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

Not Applicable

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: May 5, 2010 (Earliest date an application may be submitted to Grants.gov)
Application Due Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Due Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp and follow Steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

3.C. Application Processing

3.C.1 Submitting On-Time

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed. All applications must meet the following criteria to be considered on-time :

• All registrations must be complete prior to the submission deadline
• The application must receive a Grants.gov tracking number and timestamp (or eRA help desk ticket confirming a system issue preventing submission) by 5:00 p.m. local time on the submission deadline date.
• Any system identified errors/warnings must be corrected and the submission process completed within the error correction window.

Please visit http://era.nih.gov/electronicReceipt/app_help.htm for detailed information on what to do if Grants.gov or eRA system issues threaten your ability to submit on time.

Submission to Grants.gov is not the last step applicants must follow their application through to the eRA Commons to check for errors and warnings and view their assembled application!

3.C.2 Two Day Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

Once an application package has been successfully submitted through Grants.gov, NIH provides applicants a two day error correction window to correct any eRA identified errors or warnings before a final assembled application is created in the eRA Commons. The standard error correction window is two (2) business days, beginning the day after the submission deadline and excluding weekends and standard federal holidays. All errors must be corrected to successfully complete the submission process. Warnings will not prevent the application from completing the submission process.

Please note that the following caveats apply:

• Initial application submission must be on-time.
• The AOR/institutions is expected to enforce that application changes made within the error correction window are restricted to those necessary to address system-identified errors/warnings. NIH may reject any application that includes additional changes.
• Proof of on-time submission (e.g., Grants.gov timestamp and tracking number) and description of all changes made within the window must be documented in the PHS 398 Cover Letter component of the application.

3.C.3 Viewing an Application in the eRA Commons

Once any eRA identified errors have been addressed and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further processing.

• If everything is acceptable, no further action is necessary. The application will automatically move forward to the Division of Receipt and Referral in the Center for Scientific Review for processing after two weekdays, excluding Federal holidays.
• Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two-day viewing window. This option should be used if it is determined that some part of the application was lost or did not transfer correctly during the submission process, the AOR/SO will have the option to Reject the application and submit a Changed/Corrected application. In these cases, please contact the eRA Help Desk to ensure that the issues are addressed and corrected. Once rejected, applicants should follow the instructions for correcting errors in Section 2.12 of the SF 424 (R&R) application guide, including the requirement for cover letters on late applications. The Reject feature should also be used if you determine that warnings are applicable to your application and need to be addressed now. Remember, warnings do not stop further application processing. If an application submission results in warnings (but no errors), it will automatically move forward after two weekdays if no action is taken. Some warnings may need to be addressed later in the process.
• If the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
• If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
• Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two weekdays.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

PHS398 Research Plan Component Sections

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporate "Just-in-Time" information concepts, and follow additional requirements:

• Introduction (required for a resubmission or revision application): limited to 1 page.
• Specific Aims: limited to 1 page.
• Research Strategy, including tables, graphs, figures, diagrams, and charts: limited to 12 pages. See Table of Page Limits.

Budget Component

U.S. applicants submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) must use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component.

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year

Applicants requesting $500,000 or more in direct costs for any year (excluding consortium F&A costs) must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as plans are being developed for the study;

2) Obtain agreement from the IC staff that the IC will accept the application for consideration for award;

3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.

This policy applies to all new, renewal, revision, or resubmission applications. See NOT-OD-02-004.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations. An application that does not comply with the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)

(b) Sharing Model Organisms: Regardless of the amount requested, all applications in which the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (NOT-OD-07-088) and http://grants.nih.gov/grants/gwas/.

Foreign Applications (Non-domestic [non-U.S.] Entities)

Indicate how the proposed project has specific relevance to the mission and objectives of the NIH/IC and has the potential for significantly advancing the health sciences in the United States

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Review Process

Applications submitted for this funding opportunity will be assigned on the basis of established PHS referral guidelines for funding consideration.

Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by CSR and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

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, generally the top half of applications under review, will be discussed and assigned an impact/priority score;
• Receive a written critique; and
• Receive a second level of review by the National Cancer Advisory Board

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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 five scored review criteria, and additional review criteria (as applicable for the project proposed).

Note: Scientific innovation alone is neither the main thrust nor sufficient because innovation is complete only when delivered as new capabilities to end users, i.e., it is innovative to finish and deliver something new.

Scored Review Criteria

Reviewers will consider each of the five review criteria below in the determination of scientific and technical 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?

Does the application describe a coherent, goal oriented project likely to deliver robust new animal or human imaging or spectroscopic capabilities or tools ready for use on a targeted cancer problem in either preclinical or clinical settings?

Investigator(s). 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?

Is there evidence that the partners from academia and industry can work together effectively? Does the team engage a range of expertise and knowledge sufficient to complete the translational 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 methods, 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 methods, instrumentation, or interventions proposed?

Does the application show a coherent translational effort to deliver robust new capabilities for preclinical or clinical use? Will it deliver a new, reliable method, capacity, and/or performance to the intended user groups?

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?

Does the proposed partnership assemble complementary academic, industrial, and other expertise sufficient for better translational progress as a strategic alliance than they would achieve working separately? Does the proposed approach show translational capacity to deliver enhanced capabilities to address a targeted cancer problem for preclinical or clinical applications?

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?

Does the combined academic and industrial environment support the development and translational research aspects for the proposed work?

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, 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 subject involvement and characteristics, and 3) sources of materials.

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.

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, see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.

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.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), 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.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Revision Applications. When reviewing a Revision application (formerly called a competing supplement application), 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 address 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. As applicable for the FOA or submitted application, 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 Agents 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 (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

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

Selection Process

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. 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.

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

1. Award Notices

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 NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., Funding Restrictions.

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.

3. Reporting

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 Financial Status Report are required when an award is relinquished, when a recipient changes institutions, or when an award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Houston Baker, Ph.D.
Cancer Imaging Program
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 6060, MSC 7412
Bethesda MD 20892-7412 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 594-9117
Fax: (301) 480-3507
Email: [email protected]

James A. Deye, Ph.D.
Radiation Research Program
National Cancer Institute (NCI)
6130 Executive Plaza, EPN Suite 6015A, MSC 7440
Bethesda, MD 20892-7412 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-6111
Fax: (301) 480-5785
E-mail:[email protected]

2. Peer Review Contact(s):

None

3. Financial/Grants Management Contact(s):

Jessica Dean
Office of Grants Administration
National Cancer Institute (NCI)
6120 Executive Boulevard, EPS Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-7206
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Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants ( NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.

Policy for Genome-Wide Association Studies (GWAS):

NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices: All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.