Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

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

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of PAR-08-225

Related Notices

  • February 26, 2014 - This PAR has been expired and reissued as PAR-14-116.
  • July 17, 2013 - See Notice NOT-CA-13-011. The purpose of this Notice is to clarify specific requirements and aspects of the scientific scope.
  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
  • 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.

Funding Opportunity Announcement (FOA) Number

PAR-11-150

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.394, 93.395, 93.397

FOA 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 encourages 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.

Key Dates
Posted Date

March 14, 2011

Open Date (Earliest Submission Date)

May 5, 2011

Letter of Intent Due Date

Not Applicable

Application Due Date(s)

Standard dates apply , by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

Standard dates apply

Advisory Council Review

Standard dates apply

Earliest Start Date(s)

Standard dates apply

Expiration Date

(Now Expired February 27, 2014 per issuance of PAR-14-116), Originally May 8, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. 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 encourages 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 patient’s 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 several 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. 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 PD/PIs will be designated as lead PD/PI. The lead PD/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 explore 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 industry’s clinical decision tools: http://www.fnih.org/.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Resubmission
Revision

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

Award Budget

Application Budgets for direct costs up to $500,000 per year and project duration of up to 5 years may be requested.

Award Project Period

 Scope of the proposed project should determine the project period. The maximum period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants
 
Eligible Organizations

Higher Education Institutions:

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.  

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.   

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan

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

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign Organizations

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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 only as described in the NIH Grants Policy Statement.   

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

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.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? In addition, specific 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, 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? 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

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 evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

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

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

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

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.      

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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.

The PD(s) PI(s) will have the primary responsibility for:

The PD(s)/PI(s) 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.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

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:

Areas of Joint Responsibility include:

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:

Dispute Resolution:

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 Dispute Resolution. A Dispute Resolution Panel composed of three academic members who are not involved in the study will be convened. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.      

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Robert J. Nordstrom, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5934
E-mail: nordstrr@mail.nih.gov

James A. Deye, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5690
E-mail: deyej@mail.nih.gov

Peer Review Contact(s)

Referral Officer
Division of Extramural Activities
National Cancer Institute
Telephone: 240-276-6390
E-mail: ncirefof@dea.nci.nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Shane Woodward
Office of Grants Administration
National Cancer Institute
Telephone: 240-276-6303
E-mail: woodwars@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


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