Required Application Instructions

It is critical that applicants follow the 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

The goal of this Funding Opportunity Announcement (FOA) is to advance surveillance science by supporting the development of new and innovative tools and methods for more efficient, detailed, timely, and accurate data collection by cancer registries. Specifically, the FOA seeks applications for projects to develop, adapt, apply, scale-up and validate tools and methods to improve the collection and integration of cancer registry data and to expand the data items collected.

Applications must be built on partnership with U.S. population-based central cancer registries (a partnership must involve at least two different registries). Tools and methods proposed for development are expected to enhance the registry core infrastructure and, in so doing, expand the usefulness of registry-collected data to support high-quality cancer research.

The scientific scope of this FOA includes but is not limited to

• Development, validation, evaluation of scalable tools/methods to facilitate automatic/unsupervised extraction of specific data from various types of unstructured medical records as for example, pathology reports, diagnostic imaging, laboratory, discharge and clinical visits;
• Supplementation of cancer registries with new or more detailed data items, from existing data sources or from linkages with novel data sources, e.g. electronic medical records (EMR)

Two-phase Projects: Funds will be made available through UG3/UH3 phased innovation cooperative agreement award mechanism. Investigators responding to this FOA must apply for both UG3/UH3 phases together.

• The initial UG3 exploratory phase will be a feasibility study to demonstrate technical functionality and potential of the proposed tools/methods in a population-based central cancer registry by meeting specific performance milestones.
• UG3 projects that have met their milestones will be administratively considered by NCI and prioritized for transition to the UH3 validation phase.
• UH3 awards will support scalability, portability and implementation of the tools/methods in additional population-based central cancer registries (at least 1 more cancer registry).

Background

The NCI’s Surveillance, Epidemiology, and End Results (SEER) Program is one of the premier cancer surveillance programs in the world, composed of population-based cancer registries covering 30% of the total US population. Together, NCI’s SEER and the Centers for Disease Control and Prevention (CDC s) National Program of Cancer Registries (NPCR) collect data for the entire US population, providing national data on cancer trends and serving to identify additional needs for cancer prevention and control efforts at national, state, and local levels. In recent years, the population-based cancer registries have been facing challenges in optimally supporting cancer research optimally. Most of these challenges pertain to the increasing complexity of health care information. For example, a growing number of gene and protein-based biomarkers have been discovered and used to direct patient care, and it is crucial for cancer registries to collect this information in order to sustain the relevance of registry data to current cancer research. Hospital medical records are the traditional information source for cancer registries. With more care being delivered at outpatient facilities, it is increasingly difficult for cancer registries to collect relevant information on all cancer cases diagnosed in their catchment areas. Finally, in the future, manual processing techniques used currently by registries will be insufficient for managing the increasing volume of data (e.g., molecular imaging for precision medicine) in health care settings.

Applications to this FOA should propose to develop methods, processes, software tools or systems (collectively referred to as "tools/methods") to facilitate and enhance population-based central registries core infrastructure and data collection. The primary objectives are:

• Improving data collection methods;
• Expanding on data elements being captured (e.g. recurrence, detailed treatment, genetic profiles, risk factors) and/or captured more detailed elements (such as detailed treatment information); and
• Creating tools/methods to be incorporated in the routine process that can be scaled up to multiple registries.

Project Scope: It is expected that projects proposed for this FOA will be focused on one of the three research areas, as defined below.

Research Area 1: Natural Language Processing (NLP) or machine learning methods/tools or other methods/tools to facilitate automatic/unsupervised/minimally supervised extraction of specific discrete cancer-related data from various types of unstructured medical records.

Examples of appropriate research directions in Area 1 include:

• Design, development, and implementation of methods/tools to enable automatic/unsupervised extraction of discrete cancer-related data from unstructured free-text medical reports (such as pathology reports, radiology reports, diagnostic imaging interpretations, laboratory results, discharge and clinical visits summaries, clinic notes);
• Develop and validate algorithms to ascertain tumor molecular profiling, cancer recurrence, biomarkers, mode of detection, or risk factors (e.g., BMI, smoking) across multiple and variable medical documents;
• Develop tools/methods to integrate data in the context of cancer surveillance over a timeline of the disease progression, conforming to existing or emerging standards in the oncology and informatics domains, using machine learning methods and standardized rules developed by the NCI and partner organizations; and/or
• Develop machine assisted human review methods that combine both NLP and manual review; information is automatically extracted and stored when there is certainty that the correct information is being retrieved and recommended for manual review when the probability of a correct response is lower.

Research Area 2: Development of approaches for optimized integration of registry with various types of medical data.

Examples of appropriate research directions in Area 2 include:

• Develop approaches to link on an ongoing basis registries to multiple sources of public or private payer or administrative data sources such as Medicaid, private health insurance plans, and large managed care organizations to obtain detailed treatment information (agents, dose, frequency, subsequent course of therapy after completion of first course), comorbid conditions, or cancer patient’s health status;
• Develop approaches to link registries to existing external data sources (e.g., reportable infectious disease registries, HPV vaccination registries, clinical trial networks, or national health surveys);
• Develop approaches to link registries to large commercial pharmacy databases or other vendors/providers of products and services to obtain detailed treatment information; and/or
• Develop approaches to link to external and innovative data sources and develop methods for faster ascertainment of cancer cases and identification of cases missed by registries.

Research Area 3: Development of approaches for obtaining ongoing prospective reporting stream of data that can become part of the registry data flow

Examples of appropriate research directions in Area 3 include:

• Develop tools/methods for continuous automatic feed and/or linkage to oncology practice EHRs in order to supplement cancer registry data with a rich source of clinical data such as treatment regimens, recurrence, side effects and adverse reactions, emerging diagnostic tests, images including screening, mode of detection and reports of radiologic examinations, or genomic sequencing tests;
• Develop approaches for continuous collection of genetic or genomic test information via linkage with industry providers; and/or
• Development of tools/methods to receive data streams from laboratories on an ongoing basis.

Specific Required Project Attributes

• The investigators must partner with a U.S. cancer registry in the UG3 development phase and partner with at least one more U.S. cancer registry in the UH3 phase to ensure that the tools/methods they developed can be scaled up and implemented as part of routine data collection across the broader central cancer registry community.
• The project must have appropriate metrics and quality/assurance to evaluate the tools/methods performance.
• Tools/methods need to be suitable for sustained usage in cancer registry core processes. For example, one-time linkage with claims data are not appropriate for this FOA.
• Projects are expected to address long-term feasibility, quality, and costs associated with implementation of methods across multiple registries (beyond the specific activities proposed for UG3 and UH3 phases).
• Defined data quality assurances incorporated into standard registry operations.

Two-phase Projects: Initial cooperative agreement awards will support the UG3 phase, which is intended for pilot studies on a tool/method to be developed, validated, and implemented in a cancer registry. If the project meets the objectives and criteria described below for the UG3 phase, then the project will proceed to the UH3 phase pending review and availability of funds as described below.

Objectives for the UG3 Exploratory Phase: During the UG3 phase, the investigators must be able to develop, implement, validate tools/methods in a cancer registry. In addition, the UG3 phase should address scalability and sustainability of the tools/methods to more than one registry.

Examples of appropriate criteria (to be defined by the applicants) that will be used to evaluate the tools/methods performance:

• Criteria for Research Area 1: Accuracy, Sensitivity (Recall), Specificity, Positive Predictive Value (Precision), Negative Predictive Value, confidence estimation measures that estimate the probability that the correct information is being extracted.
• Criteria for Research Areas 2 and 3: linkage performance, impact and potential applications of the data being collected, population coverage, validation of data elements obtained through linkage

Transition from UG3 phase to UH3 phase:

After administrative review by NCI program staff, successful UG3 projects will be prioritized for selection and transition to UH3 funding.

Criteria used to determine which UG3 projects will be continued to UH3 phase will include the following:

• Demonstration that the tools/methods perform well in a cancer registry;
• Demonstration that the tool/method can be scaled-up to at least one more cancer registry;
• Evidence that the tool/method developed in UG3 phase has open-source licensing policy that can be shared by the larger registry community, for use and further development; and
• Feasibility plans for scaling the tools/methods to several registries.

Objectives for the UH3 Scalability/Portability Phase: The UH3 phase will scale up the tool/method developed under UG3 phase and prepare it for use in at least one additional population-based central cancer registry.

Expected outcomes for UH3 phase include:

• Development of tools/methods that will improve efficiency, standardization, timeliness, completeness, expansion and flexibility in data collection. Tools that will facilitate future integration of novel data sources as they are discovered and collected in clinical documents.
• Implementation of an open-source licensing policy for the tools/methods proposed in a fashion that will promote tool/method sharing and further development across the larger registry community.
• Comprehensive analyses of the costs and resources that would be needed for the implementation of the tools/methods in multiple registries in the future.
• An analysis evaluating the population representation by the new tool/method or estimating subset of cancer cases captured by the new tool/method.
• Demonstration of the scalability of the tools/methods proposed, specifically including evidence that the tool/method is generalizable across multiple registries.
• Demonstration of long term sustainability of the proposed tool/method into the routine registry operations beyond the time scale and scope of the proposed project.

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
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not 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 and based on partnerships with different (non-overlapping) population-based central cancer registries.

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).

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

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, 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:

Nadia Howlader, MS
National Cancer Institute (NCI)
Telephone: 240-276-6891
Fax: 240-276-7908
Email: howladern@mail.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

For this specific FOA, the Research Strategy section is limited to 30 pages.

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. The following additional guidance applies.

Applicants should budget appropriate travel funds for two persons (e.g., a PD/PI and another senior investigator) to attend one Investigators Meeting a year (to be held at the NCI).

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.

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

Sub-section A. Background and Significance

• Justify why the tool/method to be developed is needed and how such development can benefit, facilitate, and enhance data collection for population-based central cancer registries;
• Outline the main characteristics and applicability of proposed tool/method (identifying, for example, a specific cancer type or a specific population of focus, area of relevant cancer surveillance research) and describe the types of data elements to be captured (e.g., treatment/outcome information, recurrence, genetic profiles, biomarkers, risk factors, and other data as applicable); and
• Explain (and justify) the potential of the proposed tool/method for scaled up, wide adaptation and sustained usage by multiple cancer registries beyond the time scale and scope of the proposed UG3project.

Note: While designing the overall strategy, consider that a broad and balanced applicability of the tool/method (including coverage of various specific types of data) will be one of selection factors for programmatic priorities.

Sub-section B. Preliminary Data and Collaborative Arrangements

• Summarize prior efforts on the tool/method to be developed; indicate whether it is new or adapted from existing tools; if applicable, indicate for which areas/types of cancer-relevant data the method/tool prototype or concept has been piloted or tested;
• 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 proposed collaborations with cancer registries (e.g., identify whether newly established or extensions of previous collaborations), their scientific scope(s), and the stage of respective collaborative arrangements for the UG3project (for example, list steps completed towards building a collaborative network to share informatics solutions across registries.)

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 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):

UG3 Initial Tool/Method Development and Testing Phase

• Plans for the evaluation of such analytical aspects as:
• Tool Accuracy and Precision;
• Tool Analytical sensitivity and specificity; and
• Other analytical parameters as appropriate.
• Plans for the establishment of appropriate quality control and improvement procedures by defining how data quality assurances can be incorporated into standard registry operations;
• Approaches intended to facilitate/ensure continual feed of information or periodic linking to data source to consolidate information; and
• Approaches for exchanging reports across registries, (e.g., visualizations or quality functions on the data).

UH3 Advanced Implementation and Scale up Phase

• Describe any additional development that might be needed (beyond the UG3 phase) to optimize the tool/method as part of routine registry operations;
• Describe detailed plans to demonstrate the scalability, portability, and implementation feasibility of the tool or method developed under the UG3 phase by at least one additional population-based central cancer registry;
• Identify any plans/needs for creating infrastructure for the tool/method to be incorporated in the routine process at several registries;
• Address quality of the data and tools/methods to meet population-based cancer registry quality requirements;
• Provide an estimate of the population coverage or a special subset of cancer cases during scale up phase; 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 UG3project related to the future product development (e.g., scaling up with additional cancer registries, 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 identify a detailed project timeline. The milestones 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., (for examples of appropriate milestones, see http://imat.cancer.gov/resources/milestones.asp).

Specifically, address the following items.

• Select and present milestones as goals/benchmarks that will create go/no-go decision points in the project;
• For each milestone, provide appropriately detailed (quantitative) criteria by which milestone achievement can be assessed;
• Identify specific milestones for progressing from the UG3 phase to the UH3 phase;
• Include also yearly quantitative milestones to provide clear indicators of a project's continued progress (or signal emergent difficulties); and
• 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: For funded projects, the actual accomplishment of the milestones proposed for the UG3 phase will be a primary consideration of 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, with the following modification:

• 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.

Form only available in FORMS-D application packages for use with due dates on or before January 24, 2018.

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.

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 our Post Submission Application Materials policy.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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

For this particular announcement, note the following:

The priority of this FOA is on:

• Projects that use well-designed, robust milestones to ensure timely, efficient, and rigorous development of the proposed tool/method;
• Tools/methods that can maximize the benefits for population based cancer registries in terms of facilitated/enhanced data collection as well as a broad and balanced coverage of various relevant data types; and
• A particularly high potential for the scaled up adoption and sustainable usage of tools/methods in multiple cancer registries 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: What is the degree of relevance of the proposed tool/method to data collection by cancer registries in terms of maximizing benefits to areas relevant to cancer surveillance research as well as coverage of diverse relevant types of data? How strong and realistic is the potential of the proposed tool/method for wide and sustained usage by multiple cancer registries in the future?

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?

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?

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 efforts between the two phases of the UG3/UH3 project? Are the breadth and selection of data types to be covered broad enough and adequately balanced for the anticipated cancer surveillance research uses?

How strong are the approaches to ensure quality control and proper validation of the tool/method? Are the plans sufficient in terms of special requirements (such as meeting the quality requirements necessary for cancer registries, addressing any needs for dedicated infrastructure for the tool implementation, defining a clear path to scaling up the tool/method, etc.)?

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: Are the proposed collaborations with cancer registries appropriate and sufficient for the goals of the project? How optimal are the choices of registries and collaborative arrangements for the efforts planned for the UG3 and UH3 phases, respectively?

Milestones

Are the milestones and their associated criteria sufficient, appropriate, quantitative, and rigorous to serve as strategic "go-no go" decision points and objective benchmarks of project progress? How strong are the milestones based on which the success of the UG3 phase will be judged? How optimal are these milestones in terms of the timeliness of the development and validation of the quality of the tool/method proposed?

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.

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.

Not Applicable

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 the 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 appropriate national Advisory Council or 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;
• the balance of types of data to be captured by each project and across projects (to avoid development of duplicative tools/methods); and
• the quality, appropriateness, and rigor of the proposed milestones.

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.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 https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/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 https://www.hhs.gov/ocr/about-us/contact-us/index.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.

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 on registry data and other steps related to tools/methods implementation;
• Overseeing and coordinating the effort of the investigators 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 twice a year during the UG3 phase and quarterly during the UH3 phase updates on progress and problems in a brief format as agreed upon with the NCI; and
• Participate in webinars, annual meetings, and conference calls to share research findings with the registry community

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;
• Assisting the awardees with the implementation of their methods in central cancer registries;
• 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.

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.

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:

None; all responsibilities are divided between awardees and NIH staff as described above.

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 Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special 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.

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.

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: https://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: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

For Research Area 1 related inquiries:

Angela B. Mariotto, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6698
Email:mariotta@mail.nih.gov

For Research Area 2 and Research Area 3 related inquiries and general aspects of this FOA:

Nadia Howlader, MS
National Cancer Institute (NCI)
Telephone: 240-276-6891
Email: howladern@mail.nih.gov

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Jason Gill
National Cancer Institute (NCI)
Telephone: 240-276-6885
Email: gilljas@mail.nih.gov

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.