It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) encourages research project applications to address the development, optimization and validation of quantitative imaging (QI) software tools and methods for prediction and/or measurement of response to cancer therapies or for planning and validating radiation therapy treatment strategies in clinical trials.

The scientific scope of this FOA includes:

• Development and optimization of QI tools and/or methods for treatment planning, predicting or measuring response to therapy as open source tools that will translate into clinical trial decision support;
• Validation of the optimized tools in clinical settings to demonstrate their value for decision support in ongoing single-site or multisite clinical trials.

Two-phase Projects: A phased approach that emphasizes each of these activities must be proposed. Investigators must apply for both the UG3 and UH3 phases together in the single application.

• The initial UG3 exploratory phase is to be used for the development and optimization of QI tools and methods chosen for study by the investigating team, while the UH3 phase is for the clinical validation of the tools/methods developed in the UG3 phase.
• The UG3 phase can be no more than 2 years in duration, and the total project cannot exceed 5 years. UG3 projects will be reviewed by program staff at the termination of this phase.
• Those projects that have met their milestones may be administratively considered by NCI program staff for transition to the UH3 validation phase.

The goal of quantitative imaging is to create the condition where clinical imaging devices behave as measurement instruments, providing clinicians with reliable and reproducible numeric (i.e. quantitative) information to predict or measure the health status of patients, or to plan treatment strategies. The primary goal of this FOA, then, is to enhance the value of QI in clinical trials for treatment planning, and prediction and/or measurement of response to therapy. This can be accomplished by creating and validating state-of-the-art open source software algorithms, data collection and data processing protocols, and/or treatment planning guidelines to extract quantitative information from clinical images where the measurement bias and variance that can exist across imaging platforms have been reduced.

Projects proposed in response to this FOA are expected to advance QI methods to reduce the measurement bias and variance of imaging platforms, to create methods for extracting reliable and reproducible quantitative measurements from clinical images and/or improve treatment planning during clinical trials. The requirements for testing QI approaches in either single-site or multisite research settings have been addressed at recent NCI-supported workshops and in numerous QIN-related publications, QIN progress reports, and other documents. Note: this FOA will not support any clinical trials. It will support the cost of obtaining imaging and metadata from existing clinical trials as needed to develop, optimize and validate QI tools and methods.

For this FOA, the applicants are strongly urged to be familiar with the published research progress to date from the QIN and other research groups. For details, see the following links:

• http://imaging.cancer.gov/programsandresources/SpecializedInitiatives/qin
• NCI CBIIT HUB
• The Cancer Imaging Archive (TCIA)

Multidisciplinary research teams: The UG3/UH3 mechanism will be used to structure a phased approach to the problem of translating QI methods from development to clinical validation. Applicants should consider forming multidisciplinary research teams to address the technical activities of development and optimization of QI tools or methods in cancer imaging for the UG3 component of the research. The same or different team can be proposed to conduct the UH3 phase to validate the imaging tools in a clinical environment for eventual inclusion into the workflow of clinical trials. This research may involve evaluation of a range of multimodal imaging approaches, harmonization of image data collection, analysis, and display, as well as implementation of clinical workflow methods across imaging platforms or testing software tool performance across different cancer sites.

Each research team accepted into the Quantitative Imaging Network (QIN) (http://imaging.cancer.gov/programsandresources/SpecializedInitiatives/qin) must agree to the terms and conditions for cooperative agreements as presented in Section VI of this FOA. This network has been in existence since 2009, and information on its governance structure can be found in http://imaging.cancer.gov/programsandresources/specializedinitiatives/qin.

Project Scope/Research Objectives of the Two-Phase Projects: Initial cooperative agreement awards will support the UG3 phase, where investigators are required to develop and optimize QI tools and methods intended to improve treatment planning procedures or assess the response to therapy during clinical trials. If the project meets the objectives and criteria described below during program review at the termination of the UG3 period of performance, the project may proceed to the UH3 phase, pending availability of funds.

1. Objectives for the UG3 Development and Optimization Phase:

During the UG3 phase, investigators must focus on developing and optimizing QI tools or methods for eventual clinical utility. In addition, the UG3 phase should address opportunities and challenges such as, but not limited to, expanding the tool(s) or method(s) to different organ sites, studying the robustness of the tool(s) or method(s) to perform against degraded or inferior images, and reducing the degree of human intervention needed to use the tool(s) or method(s). If prospective clinical data are used in the development and optimization efforts, this program will not cover the costs of a clinical trial, but it will support the prospective collection of specific images and supporting data needed to develop and optimize the quantitative tools.

Activities in this phase can include participation in computational challenges. A challenge is an event organized by the network, professional societies, or other groups in which teams test the performance of tools against a specific dataset comprised of training data and test data. Goals of the challenge are established at the start, and may include improved sensitivity or specificity, speed of operation, prediction of outcome, or other quantitative result.

2. Transition from UG3 phase to UH3 phase:

After administrative review by NCI program staff, successful UG3 projects may be transitioned to UH3 phase, pending available funding.

Clearly measurable goals and milestones for the UG3 phase of the research must be included in the application. They will be used to evaluate success of the UG3 phase. Details of the transition process will be provided to the research team prior to the review.

Examples of measurable performance metrics for the UG3-phase effort might include:

• Meeting or exceeding planned measurable performance goals such as sensitivity and specificity,
• Significantly decreasing data collection time, bias and/or variance,
• Eliminating major roadblocks or handicaps to using a specific software approach,
• Demonstrating the validity of new statistical or mathematical methods in image analysis,
• Integrating other quantitative diagnostic evidence (e.g. genomic, proteomic, etc.) into functioning tools to provide measurable improvement in response prediction or measurement,
• Integrating relevant informatics methods into quantitative image analysis to achieve a measurable improvement in therapy response.

In addition, evidence that the tool(s)/method(s) are open source must be demonstrated.

3. Objectives and Expected Outcomes for the UH3 Validation and Clinical Utility Phase:

The UH3 phase will be used to validate and clinically test the optimized tools and/or methods using at least one single-site or one multisite clinical trial. Retrospective or prospective data can be used, and it is important that clinical outcome for which the tool has been developed is a part of the metadata in the analysis. Modest changes to the QI tools or methods created during the UG3 phase will be permitted, but the main focus of the UH3 phase must be on clinical validation of the QI tools. Details of the tasks to be performed in this phase must be included in the original application, but can be modified with scientific or clinical justification and program approval after UG3 review. Activities in this phase can include participation in computational challenges and in validation studies.

When tested in clinical trials, tools and methods being validated can only be a secondary measure or prediction of response to therapy, and will not be used as (nor will they interfere with) standard of care in any clinical trial. As with the UG3 phase, this program will not cover the costs of a clinical trial, but it will support the prospective collection of specific images and supporting data needed to validate the quantitative tools.

4. Duration of the Phases:

The UG3-phase can be 1 or 2 years and the total duration of the combined program cannot exceed five (5) years. The applicant will choose the durations of the phases at the time the application is submitted. See Section IV Application and Submission Information of this FOA for instructions on organizing the Research Strategy portion of the application.

Related Funding Opportunities: Research teams currently funded as a part of the Quantitative Imaging Network (PAR-14-116 [http://grants.nih.gov/grants/guide/pa-files/PAR-14-116.html] or PAR-11-150[http://grants.nih.gov/grants/guide/pa-files/PAR-11-150.html]) and interested in initiating a new research direction within the Quantitative Imaging Network may apply to this announcement with a combined UG3/UH3 application. If the existing QIN member is interested in continuing the current research effort with a competitive renewal the investigator(s) must apply through a companion announcement (PAR-17-129).

See Section VIII. Other Information for award authorities and regulations.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

New applications from current members of the Quantitative Imaging Network will be accepted through this FOA for review if the nature and goals of the proposed research are scientifically distinct from the goals of the current research effort to warrant a new project. If the current QIN member is planning a renewal of the existing research topic, application must be made to PAR-17-7610

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Robert J. Nordstrom, Ph.D.
Cancer Imaging Program
National Cancer Institute (NCI)
Telephone: 240-276-5934
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

PD(s)/PI(s) Effort: The PD/PI must include a minimum of 1.0 person month of his/her time per year. For multiple PD/PI applications, the contact PD/PI must include a minimum of 1.0 person month of his/her time per year and all other PDs/PIs must include a minimum of 0.6 person month of their time per year to the award. This commitment cannot be reduced in later years of the award.

Restricted Travel Expense Budget: Applicants must budget for travel and per diem funds for two persons (e.g., a PD/PI and another senior investigator) for each year of the project to attend one QIN Investigators Meeting per year (to be held at the NCI). Duration of the meeting will be two full days.

Budget Information Related to Collaborative Activities: Applicants must budget a set-aside of funds for annual collaborative activities in both the UG3 and UH3 phases. The use of these funds will be restricted to activities reviewed and approved by NCI program staff:

• The amounts budgeted for this set-aside should amount to 10% of budgeted direct costs in the final year of the UG3 phase of the project period and 10% of budget direct costs in each year of the UH3 phase.
• No set-aside funds will be required in the first year of a two-year UG3 effort.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

Specific Aims: Provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 phase and in the UH3 phase.

• Specific Aims for the UG3 phase must be numbered as: Specific Aim UG3-1, Specific Aim UG3-2, etc. Sub-aims should be numbered with a, b, c, etc. (e.g. Specific Aim UG3-2a).
• Specific Aims for the UH3 phase must be numbered as Specific Ain UH3-1, Specific Aim UH3-2, etc. Sub-aims should be numbered with a, b, c, etc. (e.g. Specific Aim UH3-2a).

Research Strategy: Organize the Research Strategy in the Sub-Sections A-D identified below.

Sub-section A. Background and Significance

• Justify why the quantitative imaging tool/method to be developed is needed and how such development can benefit, facilitate, and support clinical decision making during clinical trials.
• Outline the main characteristics and applicability of the proposed tool/method (identifying, for example, a specific cancer type or a specific population of focus) and describe the clinical endpoint to be captured (e.g., treatment planning-/outcome-related information, recurrence, risk factors, or other). Explain (and justify) the potential of the proposed tool/method for clinical utility beyond the UG3 project.

Note: While designing the overall strategy, consider that a broad and balanced applicability and significance of the tool/method will be selection factors for programmatic priorities.

Sub-section B. Preliminary Data and Collaborative Arrangements

• Summarize prior efforts on the QI tool/method to be developed; indicate whether it is new or adapted from existing tools; if applicable, indicate for which types of cancer it has been tried;
• If available, summarize preliminary data documenting the tool s potential to achieve both analytical sensitivity and specificity (e.g., when applied to a suitable "gold standard" source); and
• Explain the nature of the investigator collaborations within the proposed research group and collaborations anticipated with other members of the Quantitative Imaging Network.

Sub-section C. Approach

Divide this Sub-Section into two parts corresponding to the UG3 and UH3 phases, respectively.

As appropriate for each phase, describe plans to design and test the QI tools/methods, perform their analytical validation within the matrix of its intended use, etc.

These descriptions should address all the items listed below (but additional relevant aspects may also be included):

1. UG3 Initial Tool/Method Development and Optimizing Phase

• Development strategy and approach
• Plans for the evaluation of such analytical metrics as:
• Targeted accuracy and precision or other benchmarks of tool performance;
• Other analytical parameters as appropriate (e.g. speed of performance).
• Plans for the establishment of appropriate quality control and improvement procedures;
• Use of retrospective or prospective data; and
• Potential pitfalls that might occur during development and optimization and suggest solutions to them.

2. UH3 Clinical Validation Phase

• Describe any anticipated development and optimization that might be needed (beyond the UG3 phase) in preparation for clinical trial validation;
• Describe the data requirements needed to challenge the tool/method in a training/test evaluation of tool/method performance;
• Identify any plans/needs for creating infrastructure for the tool/method to be incorporated into a clinical trial;
• Provide a plan for engaging the tool/method in at least one clinical trial; and
• Identify potential pitfalls and impediments that could require a revision to the research strategy, milestones, or timeline (discuss alternative approaches/strategies, as needed, indicating whether they would require revision of the Milestones).
• Under a separate sub-heading Translational Considerations , outline your intended route/steps beyond the scope of the UG3 project related to the future product development (e.g., scaling the tool/method across other tumor types, any intentions for commercialization, any relevant interactions with commercial entities, and/or participants with business expertise).

Sub-section D. Milestones and Timeline

In this Sub-Section describe specific milestones and measurable goals for the entire project. Identify a detailed project timeline. The milestones for the UG3 phase must be well-defined to serve as appropriate objective performance targets for go/no go decision points. As a rule, milestones should be quantitative parameters, such as an appropriate level of detection, coefficient of variation, or sensitivity/specificity etc.

Specifically, address the following items:

• Select and present measurable milestones as goals/benchmarks that will create go/no-go decision points in the project to identify progress for the transition from the UG3 to the UH3 phase;
• For each milestone, provide appropriately detailed (quantitative) criteria by which milestone achievement can be assessed;
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal (use of a Gantt chart is strongly recommended).

Note 1: Reviewers will evaluate the quality, appropriateness, and rigor of the proposed milestones. To be considered for funding, applications must be viewed as strong in all these aspects.

Note 2: The accomplishment of each milestone proposed for the UG3 phase will be an important consideration for whether the awarded UG3 project should transition to the UH3 phase

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

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

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

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.

The priority of this FOA is on:

• Projects that propose a phased approach to translating quantitative imaging tools and/or methods into the clinical environment;
• Projects that use well-designed, robust milestones to ensure timely, efficient, and rigorous development and optimization of the proposed tool/method during the UG3 effort;
• Tools/methods that can enter clinical trials as a support to clinical decision making as a method to predict or measure response to therapy or as a way to plan and validate therapy regimens; and
• A particularly high potential to become a part of clinical workflow in clinical trials or standard of care beyond the timeframe of the UG3/UH3 awards.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

Specific for this FOA: Does the proposed research plan of the multi-disciplinary research team address translational research and provide a plan for quantitative imaging methods to be translated into a clinical trial setting?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

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?

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?

Specific for this FOA: Does the application propose methods for promoting translational efforts that will move technologies toward implementation in clinical trials and eventual commercial adaptation? Does the proposed research team address innovative solutions for the translation research goal of the QIN? Are the proposed clinical trials appropriate examples to substantiate the need for these methods?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific for this FOA: Given the intended usage of the tool/method and the available preliminary data, how reasonable and realistic is the division of developmental and validation efforts between the two phases of the UG3/UH3 project?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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?

Specific for this FOA: Do the participating research and clinical centers demonstrate adequate commitment to this project?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

UG3/UH3 Milestones

Milestones

Are the milestones and their associated criteria sufficient, appropriate, quantitative, and rigorous to serve as strategic and objective benchmarks of project progress?

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

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

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

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

Not applicable

Not applicable

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

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.

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).

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) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

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

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. 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:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• The programmatic selection factors will include the overall potential of tools/methods proposed for development to facilitate and enhance population-based central registries core infrastructures and data collection in a scalable and sustainable way.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) 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:

• Defining the overall research objectives and approaches;
• Determining experimental approaches, setting milestones for tools/methods development, and overseeing the conduct of analyses of data and other steps related to tools/methods implementation;
• Overseeing and coordinating the effort of the investigator's team and participating institutions to ensure optimal effort integration;
• Overseeing the conduct of UG3/UH3 research projects and ensuring their scientific rigor;
• Ensuring compliance with the applicable mandatory regulations (including protection of confidentiality of any clinical data);
• Adhering to the NIH policies regarding intellectual property, data release, and other data/resource policies;
• Submitting a comprehensive annual update report to the NCI Project Scientist (apart from the Non-Competing Progress Report RPPR and financial statements as required in the NIH Grants Policy Statement) for inclusion in the Annual QIN Overview Report.
• Participate in webinars, annual meetings, and conference calls to share research findings with the research community
• Notifying the NCI Project Staff Scientist approximately 60 days prior to the termination of the UG3 phase of the project that a review of milestones and progress must be scheduled.

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 DHHS, PHS, and NIH policies.

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

An NCI Project Scientist will be responsible for:

• Providing advice to the awardees on specific scientific, analytical, and clinical issues, as appropriate;
• Serving as a liaison between the UG3/UH3 awardees and the NCI;
• Facilitating interactions, sharing of data, and other forms of scientific integration across the UG3/UH3 awardees;
• Promoting collaborations/interactions with other NIH-supported initiatives or investigators and assisting with coordination of such efforts;
• Advising awardees with regard to various regulatory and compliance issues;
• Participating in teleconferences with PDs/PIs to monitor progress and facilitate cooperation; and
• Monitoring progress of the projects towards meeting milestones and adherence to the strategic goals of the program.
• Scheduling a committee to review the progress under the UG3 phase of the project. The review process is to be conducted and completed in accordance with Part 2 Section 1 of this FOA.

Additionally, an NCI Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This NCI Program Official will be responsible for conducting a UG3 to UH3 transition review.

NCI reserves the right to phase out or curtail an individual award (including the UH3 phase) in the event of inability to meet milestones or insufficient progress towards meeting milestones.

Areas of Joint Responsibility include:

• An Executive Committee (EC) will be the main governing board for the network. The EC will be jointly established by the lead PD/PIs of the awarded multi-disciplinary teams and selected NCI staff members.
• The EC will consist of the following voting members:
• Two representatives from each awarded team (e.g., one from the clinical center and the other from the basic science group), who will collectively have a single vote for each team; and
• Two designated NCI Program staff members (Project Scientist[s] and Coordinator), who will collectively have one vote for the NIH.
• The EC will elect one of the team investigators as its chair for a 1-year term annually during the period of the program.
• Responsibilities of the EC will include:
• Discuss progress of each team and make recommendations that encourage intra-team collaborations to enhance progress and consensus on validation methods;
• Review and facilitate the efforts aimed at sharing of validation methods and related databases across the Network;
• Review the efforts of the Research Resource teams during the course of their efforts;
• Schedule and organize an annually meeting at which network members will present their scientific progress and future plans;
• Schedule monthly telephone conference calls to coordinate the activities of the network.
• All EC decisions and recommendations that require voting will be based on a majority vote.

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 members will be convened. It will have three members: a designee of the Executive 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 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

UG3-Phase

During the UG3-phase of this project, the awardee is required to set aside 10% of the direct costs planned for the final year of the UG3 effort (i.e. year 1 for a proposed one year UG3 effort and year 2 for a proposed two year UG3 effort). These restricted funds will be released under the following conditions:

• At any time before 4 months prior to the close of the project period a plan not to exceed 5 pages must be presented to the designated NCI program staff discussing a collaboration effort with a research group within or outside the QIN network to test the performance of the optimized tool/method.
• NCI program will have 30 days to evaluate the plan and recommend changes to the plan or recommend the release of the funds.
• If changes are recommended, the investigator has 30 days to make the changes and resubmit the plan for evaluation.
• If the plan is rejected by the NCI staff at this point, the funds will not be released.

The funds may be used at the discretion of the awardee to complete the collaboration. See reporting requirements for the UG3 phase below.

UH3-Phase

During the UH3-phase of this project, the awardee is required annually to set aside 10% of the direct costs planned for that year of the project. These restricted funds will be released annually when the following conditions are met:

• At any time prior to 4 months prior to the close of a particular UH3 year, the awardee can petition to have the funds released by submitting a plan (not to exceed 5 pages) to supplement the clinical validation collaboration with research teams within the QIN network or outside the network.
• A portion or all of the set-aside funds can be requested for a specific collaboration project.
• NCI program will have 30 days to evaluate the plan and recommend the release of the funds or recommend changes to the plan.
• If changes are recommended, the investigator has 30 days to make the changes and resubmit the plan for evaluation.
• If the plan is rejected by the NCI staff at that point, the funds will not be released.

Petition for release of restricted funds can be made each year of the UH3-phase. See reporting requirements for the UH3 phase below.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)

Telephone: 301-710-0267

Robert J. Nordstrom, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5934
Email: [email protected]

Darrell Tata, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276 5894
E-Mail: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Dianna N. Bailey
National Cancer Institute (NCI)
Telephone: 240-276-6179
Email: [email protected]

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.

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 Part 75.