This notice has expired. Check the NIH Guide for active opportunities and notices.

EXPIRED

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: Quantitative Imaging for Evaluation of Responses to Cancer Therapies (U01)

Announcement Type
New

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

Looking ahead: As part of the Department of Health and Human Services' implementation of e-Government the NIH will gradually transition each research grant mechanism to electronic submission through Grants.gov and the use of the SF 424 Research and Related (R&R) forms. For more information and an initial timeline, go to http://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-035.html. NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts (http://grants.nih.gov/grants/guide/index.html).

Program Announcement (PA) Number: PAR-08-225

Catalog of Federal Domestic Assistance Number(s)
93.394, 93.395, 93.397

Key Dates
Release/Posted Date: August 1, 2008
Application Due Dates: Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
Peer Review Dates: Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Dates: Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Dates: 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: Changed to May 8, 2011 (Per NOT-OD-11-048); Original Date September 8, 2011

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

Purpose. This funding opportunity announcement (FOA) is designed to promote research on quantitative imaging of tumor response to cancer therapies in clinical trial settings, with the overall goal of facilitating clinical decision making. Proposed projects should include the appropriate development and adaptation/implementation of quantitative imaging methods, protocols and software solutions/tools (using existing commercial imaging platforms and instrumentation), and their application in current and planned Phase 1-2 clinical therapy trials. No support for the clinical trials, as such, will be provided under this FOA. The proposed projects must focus on imaging-derived quantitative measurements of responses to drugs and/or radiation therapy, and/or image-guided interventions. It is anticipated that these research goals will require multidisciplinary efforts. Therefore, this FOA solicits applications from multi-disciplinary teams to include oncologists as well as clinical and basic imaging scientists. The involvement of industrial partners in the development of the quantitative imaging methods is not required, but is strongly encouraged. Awardees will form a Quantitative Imaging Network (QIN) to share ideas and approaches to validate and standardize imaging data and related imaging metadata for quantitative measurements of responses to cancer therapies.

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

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
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) is designed to promote research and development of quantitative imaging methods for the measurement of tumor response to therapies in clinical trial settings, with the overall goal of facilitating clinical decision making. Proposed projects should include the appropriate development and adaptation/implementation of quantitative imaging methods, imaging protocols, and software solutions/tools (using existing commercial imaging platforms and instrumentation) and application of these methods in current and planned Phase 1 and 2 clinical therapy trials. The proposed projects must be focused on imaging-derived quantitative measurements of responses to drugs and/or radiation therapy, and/or image-guided interventions (IGI). It is anticipated that these research goals will require multidisciplinary efforts. Therefore, this FOA solicits applications from multi-disciplinary teams to include oncologists as well as clinical and basic imaging scientists. The involvement of industrial partners in the development and adaptation/implementation of quantitative imaging methods to aid cancer therapies is not required, but is strongly encouraged.

In order to maximize the sharing of ideas and approaches to validate and standardize imaging data and related metadata for imaging-based quantitative measurements of tumor responses to cancer therapies, the awardee teams will be required to participate and collaborate in an NCI-supervised organizational structure to be called the Quantitative Imaging Network (QIN).

Regarding the clinical trial component, the FOA will support only the development and adaptation/implementation of quantitative imaging endpoints (including imaging methods and related software tools research, and/or informatics infrastructure, as needed). Eligible clinical trials may be ongoing or planned, but these trials must be funded through other sources. Therefore, no support for the clinical trials, as such, will be provided under this FOA.

In addition, in connection with FOA, the NCI will NOT support

Alternative/Related Funding Initiatives

Investigators seeking support for imaging clinical trials, as such, are referred to the following initiatives:

Investigators seeking to validate or optimize prototype imaging hardware and methodologies for in vivo or animal studies, are encouraged to consider PAR-07-214 (http://grants.nih.gov/grants/guide/pa-files/PAR-07-214.html).

Research on early-stage imaging technology development and testing, can be supported by the traditional NIH R01 or R21 grant mechanisms.

Background

Challenges for the quantitative assessments of therapeutic responses. Advances in molecular medicine offer the potential to move beyond traditional cytotoxic anticancer treatments and develop safer and more effective targeted therapies based on molecular characteristics of a patients tumor. This opportunity is recognized by the NCI Clinical Trials Working Group (CTWG; http://integratedtrials.nci.nih.gov/ict/CTWG_report_June2005.pdf). However, significant translational research efforts are needed to realize these emerging opportunities. These efforts must include the development of improved imaging methods and protocols for quantitative assessments of therapeutic responses. Such quantitative assessment may require the use of multiple imaging modalities. The development of anatomical, functional, and molecular imaging methods requires proper recognition and addressing of the complexities associated with the expression of suspected biomarkers. Moreover, a full understanding of the response patterns for the potential surrogate biomarkers (e.g., those used to monitor angiogenesis, hypoxia, and necrosis) may often require the use of modeling and/or multiparametric analysis of the image data to examine quantitative correlations with other clinical metadata and clinical outcomes. These requirements generally hold for the measurements of tumor responses to drugs or radiation therapy, and image-guided interventions (IGI). Requirements for these imaging approaches to aid quantitative measurements of therapeutic response, were addressed at recent NCI-supported workshops, and in related reports. Specific recommendations were formulated for measurements of therapeutic responses, using PET (positron emission tomography) and MRI (magnetic resonance imaging). These recommendations included, for example, the need for repeat measurements to determine the minimum changes that can be measured in responses to therapy in a statistically robust manner. For details, see the following links: http://jnm.snmjournals.org/cgi/reprint/47/6/1059; http://imaging.cancer.gov/reportsandpublications/ReportsandPresentations/MagneticResonance; http://www.rtog.org/; http://www.aaci-cancer.org/irats/pdfs/rider.pdf; and http://www.rthttp://www.aaci-cancer.org/irats/about_network.aspog.org/.

In addition, the increasing number of experimental oncologic therapeutic strategies has generated the urgent need to develop reliable and reproducible methods for early assessment of therapeutic responses. Addressing these needs is particularly crucial in the context of adaptive clinical trial design. Oncologists engaged in the development and implementation of clinical imaging tools and methods are often hampered by an absence of validated quantitative imaging methods.

Finally, the need for validated quantitative imaging protocols in oncology will continue to grow. For example, quantitative imaging data may be increasingly required by regulatory agencies (notably, the U.S. Food and Drug Administration (FDA; http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html) as evidence for medical utility (e.g., the efficacy of an experimental cancer drug). In addition, validated imaging approaches are typically essential to assess progression free survival (PFS). PFS data are particularly important for studies of many new targeted therapeutics expected to arrest cancer growth (but not necessarily eradicate the tumor).

Need for validation of imaging methods for the evaluation of therapeutic responses. Pertinent to any experimental therapy being investigated in a clinical trial, there is a need to develop consensus approaches for the harmonization of quantitative and statistical methods. This harmonization must be conducted for the collection of imaging data and their analysis across collection sites and commercial imaging platforms (http://usms.nist.gov/workshops/bioimaging.htm). Various performance characteristics such as signal-to-noise ratio, contrast-to-noise ratio, and spatial or temporal resolution of different devices and modalities are often platform dependent. Moreover, the performance of these platforms may often fluctuate (reflecting possible instrument drift) during the course of therapy to be monitored. The development and implementation of appropriate quantity control methods, especially those using imaging phantoms, is thus a critical requirement. This approach often includes the use of a single, multi-functional phantom or an array of phantom designs that reflect measurements based on anatomy, specific function(s), and/or specific biomolecules(s). These phantoms may be either physical or computer-simulated. Both kinds are often designed and utilized to reveal temporal fluctuations in instrument performance. The phantom-based measurements and their evaluation are thus vitally important when the variability in instrument performance might approach the expected magnitude of the biological parameters to be measured as responses to therapy.

Need for clinical decision software tools. Quantitative imaging data that reflect responses to therapy and are correlated with clinical outcomes can provide an important basis for clinical decisions. In principle, the quantitative and objectively assessed characteristics derived from imaging experiments should be superior to the traditional, subjective (i.e., observer-based) assessments that often have high inter- and intra-observer variability. Further efforts are warranted to replace the subjective approaches with the objective assessments, Therefore, there is a critical need to develop and validate algorithms that can process collected imaging data to generate clinical knowledge for decision-making, and ideally automatically. Such algorithms are often referred to as clinical decision tools. These software tools usually involve the extraction of computed spatial features from images (generated by anatomical, functional, and/or molecular imaging methods) and/or the use of modeling methods that include both spatial and temporal characteristics. The algorithms typically have many interrelated parameters that need to be optimized prior to their use in specific clinical trials. This optimization is usually achieved through access to image databases that include pathological results or expert radiologist readings or other validation estimates such as comparison to simulated image sets. Used retrospectively, these validated data archives can be parsed in many different ways to create training and test data sets needed to benchmark the relative performance of algorithms and their clinical decision-making ability. Ideally, these datasets can be available as public archives to encourage development of more standardized methods for evaluation of clinical decision tools (go to http://ncia.nci.nih.gov/collections/). Finally, there is an opportunity to leverage support from industry, under a public-private partnership, to expand these databases for the purpose of more timely FDA approval and broad dissemination of clinical decision tools and related informatics infrastructure (http://www.fnih.org/partners/research_environment/IDRI.shtml).

Need for the standardization of software architecture. The performance of a clinical decision tool based on quantitative imaging often depends on the specific imaging platform for which it was created. This lack of transportability reduces acceptance of the quantitative methods and obscures validation procedures. One way to minimize this problem is to implement standardized open computer software architecture (one permitting plug and play software tools) for quantitative imaging tools. One of the main efforts to standardize all aspects of medical imaging and insure inter-operability is the Digital Imaging and Communications in Medicine (DICOM; http://medical.nema.org/dicom/geninfo/Brochure.pdf). DICOM Working Group 23, for example, is currently developing such standards to support inter-operability of software tools for data collection and analysis across different imaging platforms (http://medical.nema.org/Dicom/minutes/Committee/2004/2004-09-03/Approved_Work_Items/DICOM_Plug-ins_06.doc). The extension of the DICOM standard for application hosting, if approved, will reduce the dependence of software tools on specific platform configurations and will help accelerate the dissemination of commercial software tools that are FDA approved. It would be ideal to extend the applicability of the emerging standard to the clinical setting..

In connection with the cancer Biomedical Informatics Grid (caBIG)(https://cabig.nci.nih.gov/overview/), the NCI is currently supporting an open architecture/open source environment initiative, In Vivo Imaging Workspace (https://cabig.nci.nih.gov/workspaces/Imaging). This Imaging Workspace is based on an open architecture environment. It permits plug and play tools for image query, image annotation, and markup, including web-based validation of tools for image analysis using the caBIG. Several imaging companies are also exploring alternative proprietary software architectures that will potentially conform to the open architecture approach. This initiative is expected to aid efforts to develop standardized methods for validation of clinical decision tools and to assess their performance using publicly accessible archives.

Specific Goals and Requirements

General Scope of the Projects. Projects proposed in response to this FOA must be designed to develop state-of-the-art quantitative methods and for monitoring therapeutic responses. The proposed quantitative imaging methods should be based on imaging of responses to any form of oncologic therapy (namely drugs, radiation therapy, or image guided interventions [IGI]). Projects may span the development in the research settings, translation, and validation as needed, and incorporation of these solutions as endpoints into imaging protocols for current and planned Phase 1 and 2 trials in the clinical setting. The validation of imaging methods for the evaluation of therapeutic responses should be included. However, projects limited only to the validation aspects of imaging methods are NOT appropriate for this FOA. All of the proposed projects must include testing new or emerging imaging protocols and quantitative imaging methods in early phase trials (funded by other sources). All these solution/tools must be suitable for use as clinical decision software tools.

Multidisciplinary Teams. Ideally, the multi-disciplinary teams will be created to include both basic imaging research groups and clinical researchers (either within the same institution or from different institutions) as necessary to ensure that the appropriate experience in both early phase clinical trials and advanced quantitative imaging methods is achieved. Participants may include, for example, academic centers of excellence in computer science, medical physics or bioengineering, with specific experience in quantitative imaging methods, clinical decision software tools, and related informatics infrastructure. The clinical sites for data collection may include (but are not limited to) NCI-designated Cancer Centers, Specialized Programs of Research Excellence (SPOREs) or co-operative clinical trials group(s) that actively participate in the use of imaging methods in Phase 1 and Phase 2 therapy trials. The inclusion of industrial partners is strongly encouraged to help develop a broad consensus on the implementation of quantitative imaging methods/software tools that would be applicable across different imaging platforms.

To facilitate multidisciplinary interactions, applicants are encouraged to use the multiple Project Directors/Principal Investigators (PDs/PIs) option (see Section IV.2). If this option is used, it is expected that one of the PIs will be designated as lead PI. The lead PI can be affiliated with an imaging researcher (basic or translational), a clinical researcher, or a researcher from industry, as appropriate.

In light of the advances being made with multimodal imaging, it is anticipated that applicant teams may propose research that incorporates quantitative imaging protocols and methods for several imaging modalities, including anatomical, functional and molecular imaging, While this is acceptable, it is recognized that focusing on a single imaging modality by a multi-site team can also be fruitful.

Research Areas. It is strongly suggested that the proposed research plan follows the strategy listed below, with the understanding that emphasis in each area may vary depending on the selection of clinical trial(s) and imaging modalities.

a) The identification of drug, radiation therapy, and/or IGI trials that would benefit from quantitative imaging methods and improve prognostic outcome, including the development and optimization of clinical trial protocols, specifically to implement quantitative imaging methods;

b) The development of quality assurance methods to test and characterize time related changes in imaging systems and IGI platforms during the course of therapy;

c) The development of algorithms, modeling and image simulation methods, and related databases to validate clinical decision software tools with the goal of improving the ability to measure the response of targeted tumors to therapy quantitatively. Ideally, these tools should be developed for a range of imaging methods and validated against existing public web accessible databases. The intent is to explore consensus methods for validating clinical decision tools. See Section VI. 2.A.3 regarding the function of the Steering Committee in this regard for the QIN.

d) The development of software architecture, designed to allow interoperability of software tools that may include open source approaches. The long-term goal should ideally include harmonizing data collection, analysis, and image display across different commercial imaging, therapy, and IGI platforms. Equivalent methods such as proprietary methods and solutions supported by industry are appropriate. All the methods proposed should ideally meet emerging NCI caBIG requirements and/or DICOM 23 requirements, if and when available.

To meet the goals of this FOA, each applicant team is expected to engage oncologists in the evaluation process to accept quantitative imaging for clinical decision making in clinical trials for appropriately targeted therapies. Examples of appropriate research goals to be accomplished by the end of year 5 of the projects include (but are not limited to) the following:

a) Completion of quantitative imaging studies incorporated into two or more Phase 1 and 2 clinical trials. This goal must properly address the important aspects of patient accrual and data analyses. Validation with patient outcome can take significantly longer than the duration of this program.

b) Improved consensus and rationalization for employing and optimizing quantitative, multi-modal, and molecular imaging methods for therapies where they are clinically useful;

c) Public registries and image database resources to support clinical decision making for therapies by the broader oncology community (i.e., NCI Community Cancer Centers Program [NCCCP], NIH Clinical Trial Science Awards, etc.); and

d) Replacement of observer or qualitative estimates of therapy response, such as the use of the RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

Plans for progressive validation of these components for targeted of Phase 1 and 2 trials must also be described.

Awarded teams will be formed into a network for the purpose of sharing plans for validation and standardization of the assessment of the performance of software tools and to report clinical results in the use of quantitative imaging as a measure of therapy response. The network will be governed by a steering committee as described in Section VI 2.A.3 of this FOA.

The use of validation methods and software tools in response to this FOA must address the issue of compatibility with the NCI caBIG informatics initiative https://cabig.nci.nih.gov/). One of the goals of the caBIG (specifically, the caBIG imaging archive and workspace initiative) is to stimulate the development of open source informatics tools and open access to bioinformatics resources and data bases. These attributes should facilitate data integration and analysis over a broad range of data collection platforms covering imaging, genomic, and proteomic resources. Compatibility with caBIG components will aid investigators to consider the importance of other longitudinal biomarker data in response to therapy. This will give greater breadth to the research applicability. (https://imaging.nci.nih.gov/ncia/).

During the course of this program, the NCI may exlore the possibility of creating a Public-Private Partnership (PPP) with the imaging and pharmaceutical industry communities to be mediated through the Foundation NIH (FNIH, http://www.fnih.org/. The long-term goal and rationale for this PPP would be the creation of an extended public database and related resources of image data, meta-data, and clinical outcome data collected from sites that are funded through the FOA. These resources could be leveraged through the PPP to facilitate more timely FDA approval of industrys clinical decision tools: http://www.fnih.org/.

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 U01 award mechanism. The Project Director/Principal Investigator (PD/PI) will be 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 non-modular budget formats.

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.

This is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

The NCI intends to reissue this funding opportunity after the closing date for this present opportunity.

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.

It is required that requests for support submitted in response to this FOA should not exceed $500,000 (direct costs) per year. Facilities and administrative 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:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution 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, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, 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 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 will require additional information, as outlined in the instructions below. When considering multiple PDs/PIs, 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

Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). Since this is a new FOA, this provision is not applicable to the first receipt cycle after FOA release.

No renewal applications will be accepted.

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

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. 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

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

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:

In addition, for applications from foreign organizations:

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 U.S. or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide Items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new 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).

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Application Receipt Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Dates: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm.

3.A.1. Letter of Intent

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

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant application forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (for U.S. Postal Service express or regular mail)
Bethesda, MD 20817 (for non-USPS delivery)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix materials must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Blvd, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 4496-3428
FAX: (301) 402-0275
Email: [email protected]

3.C. Application Processing

Applications must be submitted on or before the application receipt/submission dates described above (Section IV.3.A.) and at http://grants.nih.gov/grants/dates.htm.

The NIH will not accept any application in response to this funding opportunity 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at https://commons.era.nih.gov/commons/.

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 the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements and Information

Awardees must agree to attend two meetings annually in the Washington, DC, area and to agree to the Cooperative Agreement Terms and Conditions of Award in Section VI.2.A, Award Administration Information.

Investigators should budget for travel to two investigator meetings per year to be held in the Washington, DC, area. These 1-day meetings of the QIN Steering Committee will be held for the purpose of disseminating information regarding progress on incorporating quantitative imaging into clinical trials and other topics of interest as stated in published agendas distributed by the NCI staff before the meetings.

Research Strategy Page Limitations

The standard page limitations as found in the PHS 398 application instructions (http://grants.nih.gov/grants/funding/phs398/phs398.html) apply.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. (See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html).

Do not use the Appendix to circumvent the page limitations. An application that does not observe 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 of, and advance, 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 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 where 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 (such as 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 (NIH Guide NOT-OD-07-088 and http://grants.nih.gov/grants/gwas/).

caBIG Compatibility: The use of validation methods and software tools in response to this FOA must address the issue of compatibility with the NCI caBIG (cancer Biomedical Informatics Grid) informatics initiative (https://cabig.nci.nih.gov/). One of the goals of the caBIG (specifically the caBIG imaging archive and workspace initiative) is to stimulate the development of open source informatics tools and open access to bioinformatics resources and data bases. Applications will be reviewed, but not scored, on their compatibility with caBIG and National Cancer Imaging Archive (NCIA).

Specific Instructions for Foreign Applications

All Foreign applicants must complete and submit budget requests using the Research & Related (R&R) Budget component found in the application package for this FOA (see NOT-OD-06-096, August 23, 2006).

Section V. Application Review Information

1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

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

2. Review and Selection Process

Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI 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:

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:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, and weighted as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious impact/priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

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

Core 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 this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, and/or preventative interventions that drive this field?

In addition, specific for this FOA: Does the proposed research plan of the multi-disciplinary research team address translational research and provide quantitative imaging methods, and/or research resources as required for the advancement of the role of quantitative imaging as a biomarker for response to therapy?

Investigator(s): Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, 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?

In addition, specific for this FOA: Is there evidence that the research team members can work together effectively? Does the multi-disciplinary team have experience in quantitative imaging and in clinical trials?

Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, specific for this FOA: Does the proposed research team address innovative solutions for the role of quantitative imaging as a biomarker? Are the proposed Phase 1 and 2 clinical trials appropriate examples to substantiate the need for these methods?

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?

In addition, specific for this FOA: Does the proposed multi-disciplinary research plan utilize the unique skills and capabilities of the academic and clinical centers, including industry partners if proposed? How well can the participating research centers support the conduct of the translational research for the optimization and implementation of quantitative imaging methods as applied to therapy response?

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?

In addition, specific for this FOA: Do the participating research and clinical centers demonstrate adequate commitment to this project?

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 subjects 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.

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.

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.



In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

Resubmission Applications (formerly revised/amended 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. Remove if not applicable

Protections for Human Subjects: For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

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.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

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 score.

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.

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).

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.

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: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The impact/priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, and/or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or impact/priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing; go to the following Web sites for more information:

caBIG Compatibility: The use of validation methods and software tools in response to this FOA must address the issue of compatibility with the NCI caBIG (cancer Biomedical Informatics Grid) informatics initiative (https://cabig.nci.nih.gov/). One of the goals of the caBIG (specifically the caBIG imaging archive and workspace initiative) is to stimulate the development of open source informatics tools and open access to bioinformatics resources and data bases. Applications will be reviewed, but not scored, on their compatibility with caBIG and National Cancer Imaging Archive (NCIA).

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 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.

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 also Section IV.5. Funding Restrictions).

A formal notification in the form of an 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 (designated in Item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2.A.1. Project Director/Principal Investigator (PD/PI) Rights and Responsibilities

The PD/PIs will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PDs/PIs assume responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the U01 award in accordance with these terms and conditions of the award.

Specific rights and responsibilities will include the following:

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

The Chief of the Imaging Technology and Development Branch of the Cancer Imaging Program of NCI and the designated Program Director will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as Project Scientist and Project Coordinator, respectively (as described below). Additionally, the Program Director serving as Project Coordinator will be responsible for the normal scientific and programmatic stewardship of the award and will serve as Program Official named in the award notice. The NCI Project Scientist and Coordinator (and other substantially involved staff members that may be designated) will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

The main NCI responsibilities pertinent to the awards under this FOA include the following activities:

2.A.3. Collaborative Responsibilities

A Steering Committee (SC) will be the main governing board for the network. The SC will be jointly established by the lead PD/PIs of the awarded multi-disciplinary teams and selected NCI staff members.

The SC will consist of the following voting members:

Additional NCI and/or NIH program staff members and/or program staff members from other federal agencies (e.g., FDA, National Institute of Standards and Technology [NIST], Department of Defense [DoD]) may be added to the SC by majority vote of the existing voting committee members to serve in advisory capacity (without voting rights).

The SC may, by majority vote, add representatives from the imaging and pharmaceutical industries and scientific societies to act in an advisory capacity to the SC to encourage the development of consensus methods for imaging protocols and analysis methods and related standards -- This advisory group may be invited to SC meetings when appropriate.

The SC will elect one of the team investigators as its chair for a 1-year term annually during the period of the program.

The SC will have primary responsibility for the overall organizational oversight of the QIN and for reviewing the research goals among the teams. These responsibilities will include the following:

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590, annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement. This report should include a comprehensive technical discussion of progress. In addition to this annual report, all awardees will submit the following items.

A final progress report, invention statement, and Financial Status Report (FSR) 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; peer review; and financial or grants management issues.

1. Scientific/Research Contacts:

Robert J. Nordstrom, Ph.D.
Cancer Imaging Program
National Cancer Institute
6130 Executive Boulevard, EPN Room 6071, MSC 7412
Bethesda, MD 20892-7412 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 4496-3428
FAX: (301) 402-0275
Email: [email protected]

James Deye, Ph.D.
Radiation Research Program
National Cancer Institute
6130 Executive Boulevard, EPN Room 6018, MSC 7440
Bethesda, MD 20892-7440 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-496-6276
Fax: 301-480-5785
Email: [email protected]

2. Peer Review Contacts:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service express or regular mail)
Rockville MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
Fax: (301) 402-0275
Email: [email protected]

3. Financial or Grants Management Contacts:

Ms. Eileen M. Natoli
Office of Grants Administration
National Cancer Institute
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) 496-8791
Fax: (301) 496-8601
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Vertebrate Animals:
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 (45CFR46) 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 IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the impact/priority score.

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 http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, 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, Minorities, and Children:
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 new PHS Form 398; 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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html), investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigators NIH award. 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 (DHHS) 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 DHHS 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) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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 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 NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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/.

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