It is critical that applicants follow the Multi-Project (M) 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) is associated with the Beau Biden Cancer MoonshotSMInitiative that is intended to accelerate cancer research. Specifically, this FOA falls under a scientific priority designated by the Blue Ribbon Panel (BRP) as Recommendation A "Establish a Network for Direct Patient Engagement".

The National Cancer Institute (NCI) intends to support the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. The PE-CGS Network will include:

• Several U2C Research Centers (to be supported under this FOA); and
• One U24 Coordinating Center (to be supported under companion RFA-CA-19-046).

The overall purpose of the PE-CGS Network is twofold:

• To promote and support research on direct participant engagement approaches; and
• To use such approaches for rigorous cancer genome sequencing programs addressing important knowledge gaps in the genomic characterizations of tumors in areas such as, but not limited to:
• Rare cancers or rare cancer subsets;
• Highly lethal cancers;
• Cancers with an early age of onset;
• Cancers with high disparities in incidence and/or mortality; or
• Cancers in understudied populations.

Each PE-CGS U2C Research Center to be proposed in response to this FOA must consist of the following components:

• Administrative Core;
• Participant Engagement Unit;
• Genome Characterization Unit; and
• Engagement Optimization Unit.

In addition to conducting a Center-specific research program, PE-CGS U2C Research Centers will be expected to operate as a collaborative network. Various trans-network activities will be facilitated by the PE-CGS Network Coordinating Center (U24).

Key Definitions for this FOA:

• Cancer and/or population subset: A subset/sub-type of a specific cancer (e.g., triple negative breast cancer), or cancer in a specific population (e.g., breast cancer in Hispanic women).
• Clinical Trials: The NIH definition of a clinical trial stated in NOT-OD-15-015 applies to this FOA. A clinical trial is defined as 'research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.
• Direct participant engagement: Participant engagement is defined as an ongoing, mutually beneficial interaction between participants and researchers, where participants are included as an integral part throughout the research process: including the identification of research priorities and the design, conduct and uptake of research. In direct participant engagement, research teams interact directly with participants or caregivers (via the web, social media, collaborations with patient groups or organizations, or using other forms of outreach), not necessarily through providers or the clinical setting. In some situations, contacts/outreach may include proxies (e.g., caregivers or family members of deceased participants).
• Genomic characterization: characterizations of the genomic abnormalities in a given tumor by sequencing DNA along with characterizing the alterations at the transcriptome level by sequencing RNA.
• Highly lethal cancers: or recalcitrant cancers, defined in the Recalcitrant Cancer Research Act of 2012 as having a 5-year survival rate for affected patients of less than 20% and estimated to cause deaths of 30,000 individuals in the United States per year.
• Knowledge gap refers to a lack of (or substantial insufficiency) of genomic characterization data for a specific tumor type, or subtype, or for a specific subset of patient populations with a given tumor type/sub-type.
• PE-CGS Network: Refers to the combined effort of the PE-CGS U2C Research Centers, the PE-CGS U24 Coordinating Center and the NCI to advance the science of participant engagement and cancer genome sequencing.
• PE-CGS Network Steering Committee: Includes representatives from the PE-CGS U2C Research Centers, the PE-CGS U24 Coordinating Center and the NCI.
• PE-CGS Network External Advisory Panel: A sub-committee to the PE-CGS Steering Committee. The EAP, selected by NCI, includes nine individuals with relevant expertise to advise the Steering Committee about the scientific directions of the program.
• Rare cancers: are defined as those cancers for which the age-adjusted incidence rate is less than 15 cases per 100,000 individuals in the population.
• Study Participant: Individuals with a history of a cancer diagnosis who may be interested and eligible for voluntarily offering their tumor sample for molecular characterizations such as genome sequencing. The participants may be cancer patients actively receiving treatment or post-treatment survivors.
• Understudied populations: Understudied populations as a specific group, who may or may not be medically underserved or socially disadvantaged but whose data on cancer health risks and outcomes are currently limited. There is a lack of sufficient data on this diverse group to inform evidence-based cancer control, prevention, and intervention. The dearth of research and information for these groups underscores the urgency to improve our available data and knowledge regarding cancer risks and outcomes within these understudied populations.

Beau Biden Cancer Moonshot Initiative. NCI convened the Blue Ribbon Panel (BRP) in 2016 to provide recommendations for achieving the Cancer Moonshot's goal of accelerating progress in cancer research, now called the Beau Biden Cancer MoonshotSM Initiative. The BRP was charged with assessing the state of the science in specific areas and identifying major research opportunities that could uniquely benefit from the support of the Cancer Moonshot and could lead to significant advances in our understanding of cancer and in how to intervene in its initiation and progression. The recommendations focused on areas in which a coordinated effort could profoundly accelerate the pace of progress in the fight against cancer and were not intended to replace existing cancer programs, initiatives, and policies already underway. The BRP final report was approved by the National Cancer Advisory Board and included a recommendation to Establish a Network for Direct Patient Engagement . The 21st Century Cures Act was signed into law in December 2016 dedicating new funds to support efforts associated with the Beau Biden Cancer MoonshotSM Initiative, including support for this FOA.

In the recommendation to Establish a Network for Direct Patient Engagement , the BRP called for NCI to enlist direct patient engagement through a federated network where patients will be offered comprehensive tumor profiling . The panel further noted the importance of directly engaging with patients to facilitate participation in research and ensure patients are respected and have access to the research enterprise. Moreover, the panel stated that efforts to reach minority and underserved populations should be a high priority. This FOA is a step towards accomplishing the recommendation goals.

As appropriate for research proposed in response to this FOA, applicants are encouraged to engage a pool of scientists from diverse backgrounds, including those from underrepresented groups. In line with NIH-wide policies (NOT-OD-18-210), fostering diversity and addressing underrepresentation in the scientific research workforce are among the key components of the NCI strategy to facilitate scientific discovery and enhance innovation.

The Advances and Challenges in Cancer Genome Sequencing. Recent technological advances, in particular next-generation sequencing (NGS) technologies, have revolutionized our ability to conduct genomic characterization. For example, The Cancer Genome Atlas (TCGA) program generated a comprehensive molecular characterization of 33 tumor types, using biospecimens from over 11,000 patients. Notably, this comprehensive atlas of cancer genomic profiles allowed for the discovery of major cancer-associated genomic alterations, helping to generate novel insights into cancer biology that could be applied to develop new cancer therapies, diagnostic methods, and preventive strategies.

Currently, there are opportunities to address knowledge gaps which remain. For example, many of the hundreds of different forms of cancer have not been sufficiently characterized. Furthermore, for those cancers that have been well characterized molecularly, questions remain about the generalizability of those data due to underrepresentation of samples from specific cancer subsets and understudied populations such as racial or ethnic minorities. Finally, most current cancer genomics studies lack adequate clinical or epidemiologic data.

Addressing these gaps can be facilitated by innovative ways to directly engage participants in genomic characterization studies. Various strategies are possible for direct participant engagement (e.g., via the web, social media, collaborations with patient groups or organizations, or using other forms of outreach). Optimal approaches are likely to depend on the context of cancer/population subsets to be studied.

The Principle of Participant Engagement. The foundation for each of the proposed PE-CGS U2C Research Centers must be direct engagement of study participants (i.e., cancer patients and/or post-treatment cancer survivors). The direct participant engagement efforts must be in line with and serve the scientific goals outlined below.

Scientific Focus for PE-CGS U2C Research Centers

Knowledge Gaps and Priority Areas. Each proposed PE-CGS U2C Research Center should be centered on addressing a unique research knowledge gap in the genomic characterizations of tumors. Knowledge gaps proposed for characterization are expected to be mainly identified in several specific areas of interests (Interest Areas 1-5 below). Nonetheless, if compelling justification is available, knowledge gaps outside of these areas may also be proposed (as Interest Area 6 below).

Interest Area 1: Rare cancers or rare cancer subsets;

Interest Area 2: Highly lethal cancers;

Interest Area 3: Cancers with an early age of onset;

Interest Area 4: Cancers with high disparities in incidence and/or mortality;

Interest Area 5: Cancers in understudied populations; and

Interest Area 6: Other cancer and/or population subsets justified to be highly relevant to the goals of this FOA.

Irrespective of cancer and/or population subsets chosen, the specific gap in knowledge to address should be highly important in terms of general understanding of cancer and/or relevance to clinical oncology or public health.

Note on programmatic funding priority: The NCI intends to ensure a broad coverage across the listed priority areas. It is anticipated that no more than one application focused on a specific cancer type or cancer and/or population subset will be selected for funding. Applications relevant to Interest Area 5: "Cancers in understudied populations" may receive a particular funding preference.

Applications that address cancers diagnosed in children, adolescents, and/or young adults are encouraged (in line with the goals of the Childhood Cancer Survivorship, Treatment, Access, and Research (STAR) Act of 2018, Public Law No: 115-180).

Optional Clinical Trials. Applicants may propose behavioral studies that meet the NIH definition of clinical trials. Note that any clinical trials that include clinical development or testing of interventions for therapeutic or diagnostic or preventive purposes, evaluation of intervention safety, efficacy, clinical management, etc. are beyond the scope of the FOA.

Required Attributes of the Genomic Characterizations Proposed for U2C Research Centers

Scale of Effort. It is expected that each PE-CGS U2C Research Centers will focus on at least one cancer or population subset. Multiple cancer types (or population subsets) may be selected, as long as a sufficient number of participants can be recruited to allow for meaningful interpretations of results.

In general, it is anticipated that the required genomic characterizations will be conducted on tumor specimens from hundreds of participants. However, the proposed minimal number of unique tumors to characterize (i.e., the proposed number of participants to engage) should be sufficiently high to ensure rigorous and interpretable results for the specific research proposed.

Required Characterizations. All genomic characterizations must be conducted in parallel on tumor and normal specimens in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (state-of-the-art methods are expected).

For each cancer or population subset, the characterizations must include, at a minimum:

• Whole exome sequencing (WES);
• Low-pass whole genome sequencing (coverage of 15X); and
• RNA sequencing.

Applicants may propose additional types of genomic characterizations, if appropriate for the study focus.

Biospecimens. It is anticipated that PE-CGS U2C Research Centers will collect and use formalin-fixed, paraffin-embedded (FFPE) or fresh frozen tissue samples for tumor genomic characterizations. However, an alternative biospecimen source may be proposed if appropriate (e.g., for hematologic tumors).

Blood specimens should be proposed as a source for normal DNA, however, in situations where it is not possible to collect blood specimens, an alternative source may be proposed if appropriate.

Research Team and Main Capabilities

The proposed PE-CGS U2C Research Centers must have the following expertise and requisite capabilities in place:

• Understanding of and experience in direct participant engagement approaches;
• Experience in working with understudied groups (if applicable);
• Arrangements securing access to sufficient numbers of current patients or post-treatment cancer survivors who may be potential participants;
• Appropriate organizational and technical infrastructure for genomic characterizations (including biospecimens and associated data);
• Expertise in genomic characterizations and interpretation, oncology, return of genetic results to participants, and other relevant types of health communication.

Team Composition. Given the above requirements, it is expected that the multidisciplinary team will include an appropriate combination of such specialties as:

• Social and behavioral scientists (with expertise in direct engagement, health communication, and health literacy);
• Oncologists, pathologists (with expertise in biospecimen science);
• Molecular biologists, geneticists, and bioinformaticians (with expertise in genomic characterizations as well as integration and evaluation of "omics" data); and
• Genetic counselors

Structure of the PE-CGS U2C Research Centers

Each proposed PE-CGS U2C Research Center must include the following administrative and functional components:

• Administrative Core;
• Participant Engagement Unit;
• Genomic Characterization Unit; and
• Engagement Optimization Unit.

These components must adhere to the characteristics described below:

Administrative Core

The Administrative Core will provide the administrative support to the PE-CGS U2C Research Center leadership. The main roles of the leadership and the Administrative Core will include:

• Oversight and support of all research activities;
• Facilitating interaction among the three functional units of the Center;
• Support coordination among PE-CGS U2C Research Centers and implementation of agreed upon PE-CGS Network practices and principles;

Participant Engagement Unit

This Unit will be responsible for a direct participant engagement for the purpose of performing genomic characterization. The participant engagement strategies proposed are expected to use current state-of-the-art, culturally sensitive approaches. In addition, this unit should be designed to ensure continuous improvements to the engagement process by interactions with and adapting research findings from the Engagement Optimization Unit.

Participant Engagement Unit should be able to perform such activities as:

• Reaching appropriate candidates for participants and securing their consent;
• Obtaining requisite permissions to access archived tumor samples, pathology reports, medical records, and other relevant clinical information for participants, who will authorize such releases;
• Collecting from participants appropriate normal specimens as source of germline DNA and to serve as reference for genomic characterizations;
• Tracking and evaluating the quality of biospecimens;
• Collecting relevant sets of clinical, epidemiological, and participant outcomes data;
• Reporting research findings to participants as well as returning individual-level genetic information to those participants who are interested in receiving such data;
• Maintaining an ability to re-contact participants, e.g., to obtain follow-up clinical and/or epidemiology data.

Genome Characterization Unit

This Unit should be capable of completing all the steps required for the tumor characterizations (i.e., DNA and RNA sequencing, bioinformatic analyses and interpretations, etc.).

Specifically, the Genome Characterization Unit must be able to:

• Process biospecimens of sufficient quality for downstream laboratory analysis;
• Perform, at a minimum, whole exome sequencing (WES), low-pass whole genome sequencing (coverage of 15X), and RNA sequencing of tumor and normal specimens in a CLIA-certified laboratory using state-of-the-art methods;
• Perform quality control/quality assurance of DNA and RNA sequence data;
• Analyze and interpret sequencing data (including higher level integrations, such as with epidemiology or clinical data);
• Generate individual-level interpretation of genetic data;
• Secure storage of data, preparation of data and transmission of data to the NCI Genomic Data Commons (GDC) for subsequent sharing with the broader scientific community in a manner consistent with participant informed consent.

Engagement Optimization Unit

This Unit should be able to incorporate rigorous behavioral research on optimal approaches to participant engagement in various aspects ranging from recruitment, communication, to education about genomic characterization goals and discoveries. This unit should be also be able to examine and respond to participant preferences and needs in the context of taking part in cancer genome characterization efforts.

Specific interventions to be developed and tested should be designed to identify optimal approaches (appropriate for the cancer and/or population subset selected) for such aspects as:

• Directly reaching and communicating with potential participants about goals and values of genomic characterization;
• Engaging with understudied and/or underrepresented populations;
• Recruiting and retaining appropriate participants;
• Facilitating the gathering of reliable and high-quality data from participants;
• Determining the appropriate genetic information to share with participants;
• Effectively communicating and explaining research results to study participants;
• Other aspects of participant engagement that may need optimization.

As appropriate for the study, specific behavioral interventions proposed may constitute clinical trials as defined by NOT-OD-15-015.

All research activities/interventions to be developed by the Engagement Optimization Unit should be fully integrated with and serve the overall goals for the proposed U2C Research Center.

Required Trans-Network Collaborative Activities

All PE-CGS U2C Research Centers will be required to interact closely with the PE-CGS U24 Coordinating Center (to be supported under companion RFA-CA-19-046). Therefore, the prospective Research Center applicants are expected to read RFA-CA-19-046 and familiarize themselves with the scope and responsibilities of the PE-CGS U24 Coordinating Center.

In addition, each PE-CGS U2C Research Center will be expected to collaborate across the PE-CGS Network with other U2C Research Centers. These collaborations will be facilitated by special set-aside funds, included in the direct cost limit which may be requested, for Trans-Network collaborative projects. Such collaborative projects are intended to promote and facilitate sharing best practices, optimizing approaches, and addressing common issues across the program. For example, the Network awardees may work jointly to identify and address common challenges involved in participant recruitment, consistency of laboratory procedures (biospecimen handling, sequencing, etc.), data analysis and interpretation, as well as ethical, legal and social issues

To facilitate broader interactions, all PE-CGS awardees will be required to participate in two annual meetings, an annual Investigator Meeting and annual meeting for participants.

PE-CGS Network Governance

The Network will be governed by the PE-CGS Steering Committee. The Steering Committee will convene a PE-CGS External Advisory Panel as a sub-committee that will include a broad set of external experts and stakeholders. Details on the composition and responsibilities of the Steering Committee and External Advisory Panel are provided in Section VI.2 under Cooperative Agreement Terms and Conditions of the Award.

Non-Responsive Applications

The following types of research activities are outside the scope of this FOA and will be considered non-responsive. (Non-responsive applications will not be reviewed.)

• Research primarily focused on the pursuit of a biological mechanism through basic research that does not address gaps in the genomic characterization of tumors;
• Activities that do not include a direct participant engagement approach; and
• Applications proposing clinical trials focusing on evaluating therapeutic or diagnostic or preventive purposes, evaluation of intervention safety, efficacy, or clinical management.

Trans-Network Activities

The PE-CGS Network will function as a collaborative network allowing PE-CGS U2C Research Centers to address common issues, share best practices and lessons learned, and utilize common methods where appropriate.

See Section VIII. Other Information/span> 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 from 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

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) 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.
• o 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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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).

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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:

Leah E. Mechanic, Ph.D.
Telephone: 240-276-6847
Fax: 240-276-7920
Email: NCI_PE-CGS@mail.nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative Core)	6
Functional Unit (Use for Participant Engagement Unit, Genome Characterization Unit, and Engagement Optimization Unit)	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Participant Engagement Unit: required, maximum of 1
• Genome Characterization Unit: required, maximum of 1
• Engagement Optimization Unit: required, maximum of 1

When preparing your application, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Project Summary /Abstract: Succinctly describe the research gap to be addressed and methods of direct participant engagement. State the cancer or cancer and/or population subset selected for the study.

Project Narrative: State how the research findings and resources generated from the PE-CGS U2C Research Center are expected to further knowledge in the genomic characterization of cancer and the potential impact they may have on public health. Describe how studies performed will inform future research using direct participant engagement approaches.

Facilities & Other Resources: In addition to the information required in the standard instructions, list available facilities and/or services that can be leveraged for accomplishing the goals of the proposed U2C Center (e.g. Clinical Laboratory Improvement Amendments, or CLIA, certified laboratories, informatics/computational platforms, data storage resources, communication platforms). Specify on what basis such resources will be available to the PE-CGS U2C Research Center investigators (e.g., in-lab, freely available, fee-for-service, etc.). Provide details regarding CLIA certification for laboratories and genome characterization pipelines.

All aspects of Facilities and Other Resources should be covered here, under Overall component. Indicate, however, to which functional units the specific items listed here would be relevant (and group them accordingly).

Other Attachments: Applicants must provide the following additional materials in support of their application. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks). Each Attachment must not exceed 5 pages.

Attachment 1: A table listing of Available Partnerships and Infrastructures along with their main characteristics [use file name Partnerships and Infrastructure ].

Attachment 2: PE-CGS U2C Research Center Engagement Process [use file name Engagement Process ].

Attachment 3: Example draft consent form(s) [use file name Consent ]

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Outline the overarching, high-level vision and goals for the proposed PE-CGS U2C Research Center for the funding period, distinct from the aims of the individual functional units.

Research Strategy: In lieu of the standard Research Strategy sub-sections (Significance, Innovation, Approach), use the sub-sections defined below to present a concise overall vision and plan for the proposed PE-CGS U2C Research Center. However, applications should highlight aspects of the proposed activities of the Research Center that speak to the significance and innovation of the approach.

Sub-section A: Research Focus and Significance

Using the subheading "Knowledge Gap and Interest Area", address all of the following points:

• Define the unique research gap in the genomic characterizations of tumors that will be addressed as the focus of the proposed PE-CGS U2C Research Center and identify applicable specific Interest Area(s) (from Areas 1-6 listed in Section I);
• Provide an overall rationale for the selected specific gap in knowledge, explaining how this selection matches the requirements described in Section I Research Objectives and Main Requirements (note that a particularly strong justification is needed if the knowledge gap is in general Interest Area 6). Include the following items:

o Document the lack (or substantial insufficiency) of genomic characterization data for the knowledge gap of focus [for this aspect, refer to the current status of relevant characterizations in the publicly available genomic databases, notably those of The Cancer Genome Atlas (TCGA) program or International Cancer Genome Consortium (ICGC)];

o As background information, describe the known challenges in addressing this research gap (e.g. difficult tumor to sequence, challenges in reaching or recruiting the population of interest).

o Outline the significance and anticipated benefits from the elimination of this knowledge gap in terms of general understanding of cancer and/or relevance to clinical oncology or public health (for example, explain how this genomic characterization study may lead to insights into cancer etiology, precision prevention and therapeutic intervention strategies);

o Outline rationale for and benefits from using a direct participant engagement approach to characterize the specific knowledge gap selected.

Describe the importance and feasibility of the planned research center by addressing the following four aspects (use subheadings indicated below):

• Impact on Public Health. Describe the public health burden and impact of the proposed cancer or cancer and/or population subset (incidence/prevalence, mortality, morbidity) being studied. If relevant, describe the potential impact of the proposed cancer or cancer and/or population subset on the understudied population and/or known health disparity associated with the cancer or cancer and/or population subset. Describe how the proposed research will facilitate participants feeling respected, empowered, and motivated to participate in genomic characterization studies. Outline a vision of how the data from this research center may lead to insights into cancer etiology, precision prevention and therapeutic intervention strategies by the scientific and clinical communities in the long term.
• Collaboration with Participant and Patient Communities. Outline existing partnerships or relationships with relevant cancer patient communities, health interest groups, online health forums, community groups, or organizations, which would be leveraged in the design of the proposed research center. Provide evidence of community involvement and support for any planned community-based participatory research. Describe plans for working with partners, potential challenges, and strategies to address these challenges.
• Feasibility of Direct Participant Engagement Approach. Justify feasibility of using a direct participant approach to accomplish the aims of the genome characterization study, including potential amenability of population to direct participant engagement, number of anticipated cases to be recruited, estimates of availability of archived specimens, ability to obtain specimens for tumor and normal profiling, ability to obtain medical records, and any other aspect deemed important in this regard. Describe strategies for reaching appropriate populations.
• Synergistic Partnerships and Infrastructure for Maximizing Research. Describe existing partnerships with any organizations, researchers, ongoing initiatives, health care systems, etc., which will lead to successful completion of this genome characterization study through direct participant engagement approaches, including effectively interacting and communicating with participants, obtaining medical record and epidemiology data, acquiring normal and tumor tissue specimens, performing molecular characterization, data analysis and interpretation and sharing of data for secondary reuse by the broader scientific community.
• Usage of other relevant NCI-supported resources. Highlight any proposed interactions/partnerships with other relevant NCI-supported programs. Investigators are strongly encouraged to take advantage, whenever feasible and applicable, of such programs/resources as:
• Resources supported by the NCI Center to Reduce Health Disparities (CRCHD):

o Geographic Management of Cancer Health Disparities Program (GMaP),

o National Outreach Network (NON); and/or

o The Partnerships to Advance Cancer Health Equity (PACHE).

Note: Additional specific documentation relevant to this sub-section is requested in Other Attachments (Attachment 1).

Sub-section B: Research Center Organization and Team Integration

At a minimum, address the following aspects:

• The team structure of the PE-CGS U2C Research Center, including main lines of responsibility;
• The vision of integration of individual units into a cohesive Research Center based upon collective experience and capabilities in areas pertinent to leading, coordinating, managing and understanding the various needs of the team and the research program;
• Explain how the collective skills and expertise of team members will serve the Research Center goals, specifically including the complementary multidisciplinary scientific expertise required to address the goals related to both the molecular characterization of tumors and the direct participant engagement.

Sub-section C: Overall Approach and Structure of Research Units

Provide a biological and statistical justification for the cancer type or subset proposed by the PE-CGS U2C Research Center. The number of participants included in the tumor sequencing study needs to be justified by the frequency of the cancer or cancer and/or population subset and characteristics of the cancer type proposed to study. Applicants should discuss the overall statistical power of the proposed tumor characterization for use in answering biological and/or clinical questions.

Provide a succinct outline of the structure of each Research Unit; Participant Engagement Unit; Genome Characterization Unit; and Engagement Optimization Unit; based on the requirements described in the Research Objectives and Main Requirements section earlier. Describe the workflow from working with participants or participant groups in design of the study, recruiting participants, consenting participants, obtaining epidemiology and medical record data, maintaining regular communication with participants, sample acquisition (tumor and normal), pathology examination, molecular characterization, analysis and interpretation of molecular characterization data, integration of molecular data with epidemiology and clinical data, collecting follow up epidemiology and clinical data, reporting study findings and data back to participants, communication of study results, storing of data, and deposition of data to NCI Genomic Data Commons (GDC).

Sub-section D: Milestones and Timelines

In this sub-section, describe the following:

Overall PE-CGS U2C Research Center Milestones: Describe the timeline for the overall program with brief descriptions of how the goals of each of the proposed specific aims will be achieved annually. Milestones should include outcomes for individual participants and outcomes for research generally. The overall milestones must be well-described, specific, quantitative when appropriate, and scientifically justified. The overall milestones should be connected to the performance benchmarks or progress for each of the Research Units (see the Research Strategy section of the Participant Engagement Unit, Genome Characterization Unit, and Engagement Optimization Unit). Milestones should include clear indicators of a program's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration for funding of non-competing award years for awarded U2C Research Centers. Milestones may be revised at the time of the award with approval by NCI Program Officials.

Sub-section E: Network-wide Collaboration

PE-CGS U2C Research Centers should anticipate common issues across the network, outline potential strategies for future collaborations with other PE-CGS U2C Research Centers, and describe potential flexibility to adapt for collaborative activities. Describe how the PE-CGS U2C Research Center will plan to collaborate with other PE-CGS U2C Research Centers in the network, share best practices, and address common issues in the network. Provide details on what the U2C Research Center can contribute to the PE-CGS Network, such as unique skills or engagement strategies. In addition, describe how the PE-CGS Network could enhance the activities of the U2C Research Center. Discuss plans to work with NCI and the PE-CGS U24 Coordinating Center to facilitate any future pilot activities.

Sub-section F: Health Disparities

If applicable to the type of research being proposed, address how health disparity populations or data will be integrated into the proposed studies. Highlight, as relevant, any opportunities that, if implemented, can reduce the burden of cancer in the health disparities that currently exist. In this context, efforts are encouraged to address the needs of racially/ethnically diverse populations and those from urban and rural areas who are poor and medically underserved, who continue to suffer disproportionately from certain cancers and have higher morbidity and mortality rates.

Letters of Support: In addition to standard items, applicants must provide letters from the respective leadership official(s) in the institution(s) of the proposed PE-CGS U2C Research Center documenting specific institutional commitments to the proposed PE-CGS U2C Research Center. Letters should also be included that reflect any additional resources and partnerships that will be employed to achieve the goals of the PE-CGS U2C Research Center. Letters should include those from partnering health care institutions and any other organizations that may be involved in the participant engagement (e.g. relevant cancer patient communities, health interest groups, or organizations), but not formally part of the center.

All letters of support for the entire application should be provided under Overall component.

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, must address a Data Sharing Plan.

• The Data Sharing Plan should be provided only under the Overall component, but it should cover all the activities of the PE-CGS U2C Research Center.
• Applicants should consider pre-existing intellectual property rights associated with the use of existing informatics tools/technologies. If proprietary tools/devices are used in generating the molecular characterizations, applicants should clearly state the licensing agreement and are advised to contact NCI and seek assistance as needed from the NCI Technology Transfer Center (https://ttc.nci.nih.gov/) in determining whether such arrangements are appropriate and/or adequate.
• Addressing the Cancer Moonshot Open Access Pilot Program: Utilizing the provision outlined in the 21st Century Cures Act, NCI has established a data sharing policy for projects that are funded as part of the Beau Biden Cancer MoonshotSM Initiative that requires applicants to submit a Public Access and Data Sharing Plan that: (1) describes their proposed process for making resulting publications and to the extent possible, the underlying primary data immediately and broadly available to the public upon publication; (2) if applicable, provides a justification to NCI if such sharing is not possible. NCI will give competitive preference and funding priority to applications that comply with the strategy described here. The data sharing plan will become a term and condition of award.
• Guiding Principles for Cancer Moonshot Biobanking Activities: The goal in developing these guiding principles is to accelerate research by a) increasing the availability of biospecimens for Cancer Moonshot-related and other biomedical research through facilitation of investigator to investigator sharing of biospecimens, and b) increasing the reproducibility of Cancer Moonshot research through improved biospecimen practices and corresponding annotation. These guiding principles also seek to facilitate, where possible, increased engagement of research participants through researchers' communication of aggregate research results and, in some cases, individual genomic findings that may be medically actionable for research participants. NCI will give competitive preference and funding priority to applications that conform to the "Guiding Principles for Cancer Moonshot Biobanking Activities" (http://biospecimens.cancer.gov/programs/cancermoonshot/principles) and are consistent with the "2016 NCI Best Practices for Biospecimen Resources" (https://biospecimens.cancer.gov/bestpractices/).

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Administrative Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The PE-CGS U2C Research Center PD/PI (contact PD/PI for applications with multiple PDs/PIs) must be designated as the Administrative Core Lead.

Budget forms appropriate for the specific component will be included in the application package.

Leadership Effort Commitment: The PE-CGS U2C Research Center contact PD/PI must commit and maintain through the life of the award a minimum of 1.8 person-months of effort. For applications with multiple PDs/PIs, a minimum effort of 1.8 person-months is required for the Contact PD/PI and 1.2 person-months of effort per additional PD/PI is required. The required levels of effort may reflect an aggregate of the effort for the entire PE-CGS U2C Research Center (listed here under Administrative Core) and the efforts for other PE-CGS U2C Research Center units, as applicable.

PE-CGS U2C Research Center Administrator: Based on the complexity of the U2C Research Center, applicants may propose and budget for a PE-CGS U2C Research Center Administrator to manage day-to-day operations.

Set-Aside Funds for Collaborative Trans-Network Projects: Starting in budget period 2, a minimum of $200,000 per year (direct costs) must be allocated to a restricted fund for support of post-award collaborative projects between PE-CGS U2C Research Centers. These funds should be presented in the Other Direct Costs category under the heading "PE-CGS U2C Research Center Collaborative Project Fund". Funds will be released pending approval by NCI following discussion of proposed projects by the PE-CGS Network Steering Committee.

Travel Funds: Include funds to support travel to two annual meetings: an annual Investigator Meeting and annual meeting for participants, including for PD(s)/PI(s) and other PE-CGS U2C Research Center investigators (up to four persons).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Outline specific aims for the Administrative Core.

Research Strategy: In lieu of the standard Research Strategy sub-sections (Significance, Innovation, Approach), use the sub-sections defined below to describe the administrative and organizational responsibilities of the proposed Administrative Core. Applications should also highlight aspects of the proposed activities of the Administrative core that speak to the significance and innovation of the approaches.

Sub-section A. Leadership and Participant Engagement and Cancer Sequencing PE-CGS U2C Research Center Organization

Address the major responsibilities of the Administrative Core:

• Support activities performed by the three units of the PE-CGS U2C Research Center, spanning from outreach to participants, engagement, communication, development of study protocols, implementation of study protocols, acquisition of tumor and normal specimens, collection of medical records, abstraction of data from medical records, collection of epidemiology data, sequencing analysis and interpretation, reporting back findings and data to participants, and depositing data to NCI Genomic Data Commons (GDC);
• Foster synergy and integration of the three units of the PE-CGS U2C Research Center; provide efficiency in management of large-scale collaborative research efforts (including logistical services and organizational support) involving multiple institutions, if required;
• Support coordination among PE-CGS U2C Research Centers (implementing agreed upon practices and principles, SOPs, CDEs, etc.), including management of set-aside funds;

Outline the organization of the leadership structure and overall PE-CGS U2C Research Center structure (provide relevant organizational diagrams). Describe the lines of responsibilities, including, as applicable, the effort distribution across the participating institutions.

Sub-section B. Center Logistics and Communication

Describe the communication strategies to ensure bidirectional exchange of logistical information, findings and insights, including lessons learned and best practices between:

• PE-CGS U2C Research Units
• PE-CGS U2C Research Center leadership (multiple PD(s)/PI(s)) and additional key personnel within the Research Center
• PE-CGS U2C Research Center and across the PE-CGS Network;
• PE-CGS U2C Research Center and the PE-CGS U24 Coordinating Center; and
• PE-CGS U2C Research Center and the NCI.

State who will be the lead for each level of communication.

Sub-section C: Research Oversight and Progress Evaluation

Explain how the leadership of the Administrative Core envisions the oversight of the U2C Research Center activities. Describe how the Administrative Core will support planning and evaluation activities for the U2C Research Center, including plans for the evaluation of progress on a regular basis. Describe how these evaluations will be used to prioritize activities to ensure that the main goals of the PE-CGS U2C Research Center will be achieved in collaboration with staff from the individual Units. Progress evaluation should include consideration of outcomes for individual participants and outcomes for research. Identify potential problems and alternative strategies to accomplish PE-CGS U2C Research Center goals. Describe what action will be taken if progress is insufficient, if an overall U2C Research Center milestone or Research Unit benchmark is not met or significantly delayed.

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, must address a Data Sharing Plan.

Resource Sharing Plans should only be included in the Overall component.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Functional Unit.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Use "Participant Engagement Unit" as the title for this Unit.
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Unit Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons who are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For Units with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Unit Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in the additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Unit Co-Lead' and provide a valid eRA Commons ID in the Credential field.
• The Participant Engagement Unit Leads are expected to include investigators with hands-on experience in reaching and engaging participants, recruitment, data collection via acquisition of tumor/normal specimens, and collection/abstraction of medical record data and design of questionnaires or surveys for data collection. The Participant Engagement Unit staff should include oncologist(s), pathologist(s), genetic counselor(s) and personnel with expertise in behavior/communication science. Other key personnel may include, but are not limited to, a research coordinator, certified tumor registrar and/or laboratory technicians.

Budget forms appropriate for the specific component will be included in the application package.

Outline requested budget to accomplish activities in the Participant Engagement Unit, including the outreach, recruitment, and engagement of research participants, specimen acquisition/collection and tracking, sample validation by pathologist, data collection (including medical records data abstraction, survey administration, and collection of epidemiology data), developing patient-facing materials for results reporting, participant following-up, developing and reporting on participant-centered outcomes. The budget request may include funding for equipment, software and informatics resources. Capital equipment is generally not allowed but may be permissible with strong justification to be considered on a case-by-case basis.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Outline specific aims for the Participant Engagement Unit and provide a rationale and description of how each aim addresses the research gap in the molecular characterization of a specific cancer or cancer and/or population subset using a direct participant engagement strategy.

Research Strategy: In lieu of the standard Research Strategy subsections (Significance, Innovation, and Approach), describe the activities of the Participant Engagement Unit using the sub-sections listed below. However, applications should highlight aspects of the proposed activities of the Participant Engagement Unit that speak to the significance and innovation of the approach.

Sub-section A: Rationale

Justify the research gap in the molecular profile of a specific cancer or cancer and/or population subset to be addressed by the PE-CGS U2C Research Center and explain how the Participant Engagement Unit will reach and engage participants, inform them of the purpose of the PE-CGS U2C Research Center, and acquire tumor/normal specimens and associated data in order to fill the research gap. The description should address all expectations for the Participant Engagement Unit stated in Section I. Applicants should justify the use of a direct participant engagement strategy to facilitate addressing the research gap in the molecular characterization of the cancer or cancer and/or population subset selected for the Research Center.

Sub-section B: Direct Participant Engagement

Applicants must provide details for plans for direct participant engagement, in which participant and caregiver inputs are incorporated throughout the research process. Applicants should consult the Patient-Centered Outcomes Research Institute (PCORI) Engagement Rubric in developing their plans. Specifically, the PCORI Engagement Rubric illustrates how input from patient and stakeholder partners can be incorporated throughout the entire research process (planning, conduct and dissemination). Applicants should provide details for participant engagement including:

• Plans of engaging with study participants using current state-of-the-art approaches, including such aspects as:
  • describe how planned methods of engagement will be culturally sensitive and appropriate for the population of focus; and
  • community-based participatory research approaches, as applicable for specific research program and populations, in which communities are treated as partners with research institutions.
• Explanation of how the U2C Research Center will incorporate input from research participants in the design of specific research protocols.
• Details on how the Participant Engagement Unit will develop and report on participant outcomes (including participants perspectives on whether they felt respected, empowered, and motivated to participate in the research program).
• Plans to communicate to interested participants information about study outcomes such as:
  • summary of individual health information used in the study;
  • ongoing study updates;
  • aggregated results; and
  • lay summaries of study results and publications.
• Detail plans for reporting back information on individual genetic results. These plans should include the following:
  • Describe plans for how to elicit participant preferences in whether to receive either individual level germline and/or tumor results from this research study.
  • Detail plans for how participants that opt-in to receive germline genetic and/or tumor findings will receive a summary report of pathogenic germline variants in American College of Medical Genetics and Genomics (ACMG) cancer genes and potentially actionable somatic mutations. Plans should include reporting to participants and their oncologist and should be done through the U2C Research Center s oncologist and genetic counselor.
  • Describe plans for developing materials for reporting with guidance from NCI.
  • Demonstrate appropriate licensure for return of genetic information to participants.
  • Describe ability to modify policies and procedures to adapt to possible policy changes for the return of genetic results, as this is a rapidly evolving policy area.
• Describe how optimal engagement strategies and methods of results reporting will be iteratively informed and modified based on research findings from the Engagement Optimization Unit.

Note: Additional information is requested for this sub-section under Overall component, Other Attachments (Attachment 2 "PE-CGS U2C Research Center Engagement Process ).

Sub-section C: Tissue Acquisition and Data Collection.

Applicants should explain the details for acquiring tissue and collecting epidemiology and clinical data including:

• Explain the procedures for obtaining tumor tissue and normal specimens to be provided to the Genome Characterization Unit. Justify the source of tumor specimens. Describe plans for collection of a blood sample for germline DNA analysis. In some situations, it may not be possible to collect a blood sample. If using an alternative source of normal sample (e.g. normal tissue or saliva), applicants must demonstrate that this will reflect normal germline DNA, or is appropriate, for the characterization of the cancer or cancer and/or population subset.
• Describe how the biospecimens to be submitted to the Genome Characterization Unit will be first evaluated/verified by a trained pathologist(s)/molecular pathologist(s) to ensure that the samples meet the protocol guideline standards, including evaluation of number of tumor nuclei, percent necrosis tissue and pathology review before specimens may be used by the Genome Characterization Unit. Include parameters describing to what extent they are histologically homogeneous and what needs to be done if deviations from guideline standards occur.
• Describe process for collecting medical and pathology records, abstracting data, and compiling into a database for integration with sequencing data.
• Detail plans for collecting relevant set of epidemiological / clinical variables that would best inform interpretation of the molecular characterization of the tumor. Applicant should propose the list of epidemiology and clinical variables for collection, which will be subject to NCI approval at time of grant award. At a minimum, clinical and epidemiological variables should include, age, gender, race/ethnicity, exposure to relevant risk factors, family disease history, method of diagnosis (screen-detected, symptom-detected, incidental etc.), tissue pathology etc.
• Develop and report on participant-centered outcomes (i.e., outcomes related to individual participants such as perspectives on whether they felt respected, empowered, and motivated to participate in the research program).
• Applicants should specify methods to perform longitudinal follow-up collection of clinical and epidemiology data and approaches to capture relevant participant-reported outcomes.
• Describe process for maintaining ability to re-contact participants and obtain additional longitudinal epidemiological or clinical information.
• Provide plans for how sites will work with NCI to facilitate any pilots (e.g. with the All of Us program) focused on abstracting data from Electronic Health Records for obtaining additional clinical information.
• If appropriate, provide plans for the creation of an online website and/or portal for participants (e.g. to facilitate recruitment, communication, and providing information to participants). This portal should be integrated into the cancer.gov network for direct patient engagement portal and patient gateway currently under development. The PE-CGS U2C Research Center participant portal should help inform the development of future iterations of the NCI patient gateway.
• Describe how the Unit will adapt initial protocols based on research performed by the Engagement Optimization Unit.

Applicants must document their ability to engage and recruit participants, procure, process, track and store biospecimens and collect epidemiological and clinical data using previously developed CDEs.

Detailed biospecimen collection annotation is a requirement. The description should include information on the types of participants to be accrued, clinical and epidemiology information to be collected, and types of biospecimens to be collected.

Applicants should describe the quality assurance/quality control (QA/QC) procedures. The procedures and the documentation should include confirmation of pathology reports. The applicants must discuss their experience with relevant quality control metrics and other considerations that may arise in complex studies which may involve multiple institutions. All new biospecimen collections and storage should follow the guidelines provided in NCI Biorepositories and Biospecimen Research Branch's Best Practices.

Sub-section D: Informed Consent

In this sub-section provide details about the informed consent which will be obtained from participants. Since this study is a research study, where the molecular characterization is unlikely to provide clinical benefit to the participants in this study, careful design of consent forms is required to explain the research study to participants. In addition, consent forms must allow for broad data sharing as required by the Beau Biden Cancer Moonshot Public Access and Data Sharing Policy. Initial informed consent form may be updated based on participant feedback.

Note: Additional information is requested for this sub-section under Other Attachments (Attachment 3 "Consent Form").

Sub-section E: Performance Benchmarks

Applicants should provide a clear set of benchmarks. These benchmarks should address the aims of the Participant Engagement Unit, i.e. directing participant engagement, recruiting participants, acquiring tissue, collecting appropriate data, and communicating with and returning information to participants. Outline benchmarks that will document progress towards the achievement of the Overall Research Center milestones. Benchmarks should include consideration of outcomes for individual participants and outcomes for research. Applicants should include plans for critically evaluating and revising these benchmarks on a regular basis. The inclusion of a proposed timeline for implementing components and processes of the Unit is encouraged. In addition, applicants should describe how they will prioritize their activities to ensure that the Overall Research Center milestones of the PE-CGS U2C Research Center will be achieved. Applicants should also describe what action will be taken, and when, if a benchmark is not met or significantly delayed. In addition, applicants should identify potential problems and alternative strategies to accomplish Participant Engagement Unit goals.

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, must address a Data Sharing Plan.

Resource Sharing Plans should only be included in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions, with the following modifications:

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Functional Unit.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Use "Genome Characterization Unit" as the title for this Unit.
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Unit Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons who are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• For Units with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Unit Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in the additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Unit Co-Lead' and provide a valid eRA Commons ID in the Credential field.
• The Genome Characterization Unit Leads are expected to include investigators with expertise leading multidisciplinary teams with hands on experience in performing molecular characterization of tissue, tumor and germline sequencing, sequence analysis and interpretation. The Genome Characterization Unit staff should include, but is not limited to, personnel with expertise in pathology, DNA and RNA sequencing data generation, analysis and interpretation, bioinformatics, data integration, and data storage and sharing approaches, etc.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Detail requested budget for Genome Characterization Unit, including costs for DNA/RNA isolation and library preparation, CLIA genomic characterization, quality control/assurance, data analysis and interpretation, development of summary report for participants, uploading data to the NCI GDC, expertise in informatics and data storage, and all associated materials. Capital equipment is generally not allowed but may be permissible with strong justification to be considered on a case-by-case basis.

Note that specimens should be batched to minimize costs for genomic characterization. This budget request may include funding for equipment, software, and computing resources.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Outline specific aims for the Genome Characterization Unit and provide description and rationale of how each aim addresses the research gap in the molecular profile of a specific cancer or cancer and/or population subset using a direct participant engagement strategy.

Research Strategy: In lieu of the standard Research Strategy subsections (Significance, Innovation, and Approach), describe the activities of the Genome Characterization Unit using the sub-sections listed below.

Sub-section A: Rationale

Explain how the Genome Characterization Unit will approach conducting genomic characterization for selected cancer or cancer and/or population subset using biospecimens procured by the Participant Engagement Unit and using state-of-the-art technologies. At a minimum, sites should plan on whole exome sequencing, RNA sequencing and low-pass whole genome sequencing (15X coverage) of tumor and normal specimens acquired by the Participant Engagement Unit. Provide rationale for any additional proposed molecular characterization of tissue.

The description should also address all the other expectations for the Genome Characterization Unit stated in Section I.

Applicants should highlight aspects of the proposed activities of the Genome Characterization Unit that demonstrate the significance and innovation of the approach.

Sub-section B: Molecular Characterization, Analysis and Interpretation

Address challenges and concerns about reproducibility with the molecular characterization of DNA and RNA extracted from FFPE tissues. It is expected that the applicants will take the necessary measures to address the potential challenges and a plan for addressing potential pitfalls in the approach must be provided.

The Genome Characterization Unit should plan to work closely with the Participant Engagement Unit regarding standardization, optimization and preservation of sample integrity submitted for molecular characterization. Appropriate controls must be used for all assays.

Applicants must provide a roadmap of plans for molecular characterization of tumors and normal specimens including, but not limited to the following:

• Describe plans for molecular characterization of tumor and normal biospecimens including proposed technologies, pipelines, and workflow. NOTE: Sequencing should be performed in batches to maximize the efficiency of sequencing.
• Describe how the Genome Characterization Unit has the technical expertise to address the challenges of assay design/analysis of FFPE tumor specimens (or other source of tumor specimens), normal specimens, to reliably identify genomic alterations, actionable variants and other molecular alterations.
• Describe the best practices for the selected molecular analyses with least variability due to external and internal confounders (e.g. biases due to sample processing, batch effects, experimental reagents, study design, etc.).
• Describe QA/QC considerations; describe a strategy to monitor and ensure the quality of biospecimens, instrument performance and data generated across the Research Center. Applications should describe typical error rates for the proposed technology platforms to ensure data quality.
• Applicants should concisely indicate their metrics of DNA and RNA sequence quality.
• Describe plans for communication with the Participant Engagement Unit about any issues with biospecimen quality and needs for obtaining substitute specimens in the event DNA or RNA is of insufficient quality for sequencing purposes.
• Describe plans to establish a tight integration between the Genome Characterization Unit with the Participant Engagement Unit and the Engagement Optimization Unit to ensure adequate collection and sharing of metadata and experimental data for processing, analysis, and interpretation.
• Provide power calculations that include correction for the number of markers estimated. If there is a plan to sequence a discovery set and then validate via genotyping or custom sequencing, provide power for the validation set.
• Describe informatics plans for analysis and interpretation of molecular characterization data and integrating data with epidemiology and clinical data.
• Describe strategy for management of data (statistical and computational analysis support, study design, informatics infrastructure).
• Describe the institutional computing resources available for this study, the type of data storage and analysis platform that will be used, and how the data will be managed. Highlight the team's experience with management of large data sets (especially those similar to the one proposed for the PE-CGS U2C Research Center) beyond information described on the biographical sketch. Also describe strategies to maintain data security.
• Detail plans for interpretation of genetic data for return to participants. PE-CGS U2C Research Center investigators are encouraged to use automated informatics pipelines for interpretation of pathogenic germline or potentially actionable somatic mutations for use in a summary report that will be provided to participants that have requested return of genetic data. As part of program activities, each PE-CGS U2C Research Center is expected to share information about algorithms used for interpretation and will be encouraged to share informatics tools.
• Describe plans for uploading data to the NCI GDC.

Sub-section C: Preliminary Data

Use this sub-section to present preliminary data addressing, minimally, the following aspects of the Genome Characterization Unit:

• Demonstrate the current capacity within the Genome Characterization Unit using the proposed technology platforms, especially for research similar to the one proposed.
• Provide appropriate information if the proposed research requires a Food and Drug Administration (FDA) Investigational Device Exemption (IDE). IDE may be needed for new sequencing methods, (separate from the requirement for the test to have been conducted within a CLIA-certified environment). Investigators must be prepared to discuss the possible need for an IDE with their IRBs and document the outcome of those discussions, and to subsequently engage in pre-submission discussions with the FDA if the IRB determines they are needed. These typically involve submission of actual study protocols, including the entire sequencing pipeline from sample preparation to return of results. Applicants may wish to consult the following Points to Consider in Assessing When an Investigational Device Exemption (IDE) Might be Needed: http://www.genome.gov/27561291 .
• Prior experience working with the laboratory that will conduct the proposed variant analysis, interpretation and results reporting should be described.
• For studies proposing to use novel technologies, appropriate preliminary data for each technology should be provided.
• If technology platforms are located across institutions, provide a demonstration of the proposed workflow.

Sub-section-D: Performance Benchmarks

Applicants should provide a clear set of benchmarks. These benchmarks should address the aims of the Genome Characterization Unit, i.e. tissue processing, genome characterization, analysis and interpretation, and uploading data to NCI GDC. Outline benchmarks that will document progress towards the achievement of the Overall Research Center milestones. Applicants should include plans for critically evaluating and revising these benchmarks on a regular basis. The inclusion of a proposed timeline for implementing components and processes of the Unit is encouraged. Applicants should describe how they will prioritize their activities to ensure that the Overall Research Center milestones of the PE-CGS U2C Research Center will be achieved. Applicants should also describe what action will be taken, and when, if a benchmark is not met or significantly delayed. In addition, applicants should identify potential problems and alternative strategies to accomplish Genome Characterization Unit goals.

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, must address a Data Sharing Plan.

Resource Sharing Plans should only be included in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Functional Unit.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Use "Engagement Optimization " as the title for this Unit.
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Unit Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons who are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• For Units with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of 'Other (Specify)' and designate the role under 'Other Project Role Category' as 'Unit Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in the additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Unit Co-Lead' and provide a valid eRA Commons ID in the Credential field.
• Unit Leads are expected to have with significant expertise and hands-on experience in communication research and direct engagement with research participants.
• The Unit must have senior/key investigators with expertise in social and behavioral science, including experience in conducting health communication and health literacy research.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Outline requested budget for research activities for the Engagement Optimization Unit. Budget may include pilot data design and data collection, research protocol development and implementation, survey administration and other methods of gathering data on participant preferences and input, and communication and public relations expertise. This budget request may include funding for web development and design, social marketing strategies and tools, data analytics, equipment, software, and computing resources.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Outline specific aims for the Engagement Optimization Unit and provide a rationale and description of how each aim addresses the research gap in the molecular profile of a specific cancer or cancer and/or population subset using a direct participant engagement strategy.

Research Strategy: In lieu of the standard Research Strategy subsections (Significance, Innovation, and Approach), describe the activities of the Engagement Optimization Unit using the sub-sections listed below. However, applications should highlight aspects of the proposed activities of the Engagement Optimization Unit that speak to the significance and innovation of the approaches.

Sub-section A: Rationale

In this section, applicants should explain how the Engagement Optimization Unit will approach the performance of rigorous empirical research on participant engagement, recruitment, communication, and education about genomic characterization research goals and discoveries. Specifically, describe the empirical research problem, which will be examined by this unit. In addition, provide rationale for these studies in participant engagement and communication by addressing the following:

• Describe current gaps in understanding in participant engagement and/or communication with regards to genomic characterization.
• Outline key research objectives in the development and testing of innovative approaches for participant engagement and communication as outlined in section on Research Objectives and Main Requirements for the Engagement Optimization Unit.
• Provide sound rationale from current literature and preliminary research findings (if available) for the proposed approach.
• Describe unique challenges and opportunities in participant engagement and communication for genomic characterization research studies
• Describe key process measures and communication outcomes and provide a conceptual framework for how various outcome measures may connect to one another.
• Describe how the results from this unit, or enhanced participant engagement and communication, could facilitate future data collection towards the goals of improving molecular characterization of cancers or cancer and/or population subsets.
• Explain approaches considered to facilitate participants feeling respected, empowered, and motivated to participate in cancer research genomic characterization studies.
• Identify how addressing these questions in participant engagement and/or communication will advance cancer research in general (i.e. lessons that may be applied beyond genomic characterization studies).

Sub-section B: Approach to Address Research Questions

In this sub-section, applicants should identify an initial set of empirical research questions in participant engagement and communication and provide plans to address these questions. Explain measures to ensure that plans are flexible and adaptable to ongoing research and implementation needs, including needs to modify initial questions or identify additional empirical questions. Plans should also include the following:

• Describe the key research questions and the planned study design. Explain how this study design will address the empirical research questions in participant engagement and communication.
• Outline approach to iteratively revising research questions, including modifying questions and/or adding new empirical research questions depending on, for example, findings from preliminary research, PE-CGS Network best practices, or changes in policies (i.e. changes in policy expectations for the return of genomic research results).
• Define and describe major study outcomes and intermediary outcomes and how they will be measured.
• Provide details about the population being studied, including estimated number of participants, planned race/ethnicity, geographic, and sociodemographic distribution, and other participant characteristics.
• Applicants are encouraged to use a mixed methods approach, as appropriate, in order to integrate quantitative and qualitative insights.
• In performing observational study or behavioral clinical trial, provide estimate of power to detect associations with sample size and provide a sample size justification.
• Describe plans for analysis and interpretation of findings.
• Describe plans for being nimble and adaptive to accommodate research findings and modify procedures for the Participant Engagement or Genome Characterization Unit.

Since several empirical questions may be included in this unit, details about the approach should be provided for each question proposed in participant engagement and communication to be addressed.

Sub-section C: Plans for Integration with Participant Engagement Unit and Genome Characterization Unit

In this section, applications should outline plans for how results from the Engagement Optimization Unit will be used to inform the protocols developed by the Participant Engagement (e.g. design of consent, recruitment procedures) and Genome Characterization Unit (e.g. informing the generation of the genetic data report for participants).

Sub-section-D: Progress Evaluation

Applicants should provide a clear set of benchmarks. Outline benchmarks that will facilitate progress towards the achievement of the Overall Research Center milestones. Benchmarks should include consideration of outcomes for individual participants and outcomes for research. Applicants should include plans for evaluating research progress on a regular basis. Applicants should describe how they will prioritize their activities to ensure that the Overall Research Center milestones of the PE-CGS U2C Research Center will be achieved. The inclusion of a proposed timeline for implementing components and processes of the Unit is encouraged. Applicants should also describe what action will be taken if research progress is insufficient or significantly delayed. In addition, applicants should identify potential problems and alternative strategies to accomplish research studies planned for the Engagement Optimization Unit.

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, must address a Data Sharing Plan.

Resource Sharing Plans should only be included in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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 and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the PE-CGS U2C Research Center 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 PE-CGS U2C Research Center 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 PE-CGS U2C Research Center that by its nature is not innovative may be essential to advance a field.

Does the PE-CGS U2C Research Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the PE-CGS U2C Research Center 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 to this FOA: How well does the PE-CGS U2C Research Center address a knowledge gap, defined as performing genomic characterizations of tumors that are currently not well-covered (i.e. characterized with a sufficient number of cases for meaningful interpretation of sequencing results by prior efforts such as TCGA or ICGC)? How well is the proposed research aligned with the areas of interest and goals defined for this FOA? Will the proposed participant engagement strategy result in participants feeling respected, empowered, and motivated to participate in this research program? Will study accomplishments lead to insights into optimal approaches to participant engagement, outreach, and communication in genomic characterization studies?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the PE-CGS U2C Research Center? 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 to this FOA: Do the PE-CGS U2C Research Center PD(s)/PI(s) and other key personnel have the necessary expertise, experience, and understanding of the design, administration, and analysis of the multi-disciplinary research program? How well do the proposed collaborations between the PE-CGS U2C Research Center PD(s)/PI(s), Unit Leads, and other key personnel integrate the components and advance genomic characterization? Do the investigators demonstrate relevant experience with participant engagement in diverse, minority and understudied populations and settings as appropriate? Do the PD(s)/PI(s) have experience with collecting, analyzing, and publishing phenotypic and genomic data, and with returning genomic results to participants?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the program, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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 to this FOA: Does the plan for participant engagement, education and communication employ novel concepts, approaches, methods, and/or platforms?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the PE-CGS U2C Research Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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?

If the PE-CGS U2C Research Center 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: Does the application include adequate plans to recruit and retain the proposed numbers of diverse participants, minority, or understudied populations, as appropriate for the cancer type or subset selected for study? Are the participant engagement plans feasible for the selected cancer or cancer and/or population subset? Does the research center include adequate plans for reporting back data and study information to participants? How are the Overall PE-CGS U2C Research Center milestones designed to ensure successful completion of the proposed genomic characterization using direct participant engagement approach? Does the application include adequate plans for integration across units and for collaborating across the network? How acceptable are the plans for addressing the NCI Cancer Moonshot Public Access and Data Sharing Policy?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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 to this FOA: Are appropriate resources available to engage diverse participants and populations, as appropriate?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Reviewers will provide only one overall adjectival rating for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the PE-CGS U2C Research Center?
• How well will the structure of the Administrative Core promote communication between the various Research Center components? Do the Administrative Core plans facilitate synergy across the Research Center units?

Reviewers will provide only one overall numerical score for the Participant Engagement Unit (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• Do the unit leads have appropriate experience and does the unit have staff with appropriate expertise for the goals of the Participant Engagement Unit?
• Are adequate plans provided for direct participant engagement?
• Are appropriate procedures and quality control plans proposed for the activities of the Participant Engagement Unit?
• Are there adequate plans for disseminating information back to participants and returning genetic information, as appropriate?
• Are there adequate plans for incorporating information learned from the Engagement Optimization Unit?
• Are potential problems, alternative strategies, and benchmarks for success presented?

Reviewers will provide only one overall numerical score for the Genome Characterization Unit (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• Are the Unit Leads, collaborators, and other researchers well suited to the goals of the Genome Characterization Unit?
• Are plans for performing genome characterization including technology, pipelines, quality control and quality assurance procedures, and workflow likely to be successful?
• Are sequencing protocols optimized to maximize the efficiency of sequencing (e.g. batching of specimens when appropriate)?
• How well does the preliminary data provided demonstrate that the Genome Characterization Unit can perform the sequencing and other molecular technologies proposed for this study?
• Are plans for interpretation of genetic data for return of data to participants sufficient and adaptable?
• Are potential problems, alternative strategies, and milestones for success presented?

Reviewers will provide only one overall numerical score for the Engagement Optimization Unit (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• Are the Unit Leads, collaborators, and other researchers well suited to the goals of the Engagement Optimization Unit?
• Does the application address the development and testing of innovative interventions to identify optimal approaches for participant engagement and communication?
• Will the proposed research facilitate participants feeling respected, empowered, and motivated to participate in cancer research sequencing studies?
• Is the approach for addressing the research questions on participant engagement and communication likely to be successful?
• Will results from the Engagement Optimization unit directly inform protocol development of the Participant Engagement and Genome Characterization Units?
• Are potential problems, alternative strategies, and milestones for success presented?

As applicable for the PE-CGS U2C Research Center 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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the program incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the 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 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 PE-CGS U2C Research Center 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 individuals of all ages (including children and older adults) 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 program.

Not Applicable

Not Applicable

As applicable for the U2C Research Center 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 .

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 will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned 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.

o To ensure a broad coverage across the listed areas of interest, it is anticipated that no more than one application focused on a specific cancer type or cancer and/or population subset will be selected for funding. In addition, applications focused on cancers in understudied populations may receive a particular funding preference.

o Compliance with Beau Biden Cancer Moonshot Open Access and Data Sharing Policy

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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety

Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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 https://www.hhs.gov/civil-rights/for-individuals/section-1557/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 https://www.hhs.gov/civil-rights/for-individuals/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.

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 Part 75.

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 program 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:

• Overseeing the scientific research in the PE-CGS U2C Research Center, analyzing and interpreting research data, reporting results to the scientific community, and disseminating approaches, methods, software, and tools broadly.
• Committing and maintaining throughout the life of the PE-CGS U2C Research Center a minimum of 1.8 person-months of effort per year for the investigator designated as the contact PD/PI.
• Committing and maintaining throughout the life of the PE-CGS U2C Research Center a minimum of 1.2 person-months of effort per year for any investigator designated as a non-contact PD/PI of the PE-CGS U2C Research Center.
• Agreeing to be an active participant in the PE-CGS Network, including attending the annual network meetings and participant centered meetings, participating in other network sponsored meetings, webinars and workshops, and participating in collaborative activities.
• Serving on the PE-CGS Network Steering Committee. The PE-CGS U2C Research Center PD/PI (contact PD/PI for applications with multiple PD(s)/PI(s)) is required to serve as a member of the PE-CGS Network Steering Committee.
• Abiding by the governance of the PE-CGS Network and all program policies agreed upon by the PE-CGS Network Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations.
• Reporting progress to the NCI Program Officials on all PE-CGS U2C Research Center research and outreach activities annually. In addition to standard annual Research Performance Progress Report (RPPR) submissions, Principal Investigators may be expected to supply additional progress-related information.
• Being prepared for ad hoc site visits of NCI Program staff members and participation in the NCI-coordinated evaluation of the PE-CGS Network. The Administrative Core should coordinate participation in PE-CGS U2C Research Center program evaluation activities, including generation of progress reports and logistics of site visits.
• Leveraging, where feasible, technology from related NCI-sponsored informatics initiatives, for example the NCI Informatics Technology for Cancer Research (ITCR) program, which supports the development of informatics algorithms, tools, and resources across the continuum of cancer research.
• Coordinating with and leveraging, where feasible, the technology of the NCI Cancer Research Data Commons, a program that will provide infrastructure to make diverse cancer research data broadly available and to maximize their reuse and impact.
• Ensuring that data are deposited in a timely manner to the NCI GDC, and software and other tools and resources developed as part of this Research Center are made publicly available according to PE-CGS policies and in accordance with the Beau Biden Cancer Moonshot Public Access and Data Sharing Policy. Additionally, all PE-CGS U2C Research Centers will be required to utilize the resources within the PE-CGS U24 Coordinating Center, including communication materials, common data elements, and metadata dictionaries developed in collaboration with PE-CGS investigators.
• Ensuring that participants are engaged in the research and feel respected, empowered, and motivated to participate in the PE-CGS research study.
• Ensuring that results of the PE-CGS U2C Research Center are published in a timely manner.

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.

PE-CGS U2C Research Center investigators will also be encouraged to participate, as appropriate, in other PE-CGS meetings and workshops, collaborative activities, and/or scientific and programmatic working groups.

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

One or more designated NCI Program staff members will have substantial involvement as Project Scientist(s) for the PE-CGS U2C Research Center.

Additionally, an NCI Program Director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Program Officials may also have substantial programmatic involvement (as Project Scientists).

The specific roles of the substantially involved NCI staff members include the following activities:

• Serving as voting and non-voting members of the PE-CGS Network Steering Committee.
• Assisting the PE-CGS Network Steering Committee, the PE-CGS U24 Coordinating Center, and individual PE-CGS U2C Research Center awardees in avoiding unwarranted duplications of effort across the PE-CGS Network.
• Facilitating collaborative research efforts that involve multiple PE-CGS U2C Research Centers and would be suitable for consideration as a trans- PE-CGS Network collaborative project to be funded by restricted Research Center collaborative funds.
• Supporting the awardees as a resource in facilitating their broader interactions with other NCI and NIH programs to disseminate results, tools, and best practices from the PE-CGS U2C Research Centers and take advantage of existing NIH/NCI resources and infrastructures.
• Monitoring the operations of the PE-CGS Network awardees and making recommendations on overall program directions and allocations of PE-CGS U2C Research Center funds.
• Participating in organizing annual PE-CGS investigator meetings, participant centered meetings, specialized workshops, and webinars of the network.

In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the National Cancer Institute (NCI) will monitor and evaluate progress to meet the expectations set forth by Congress in the 21st Century Cures Act.

Areas of Joint Responsibility include:

PE-CGS Network Steering Committee. The PE-CGS Network Steering Committee will be the main governing body for the PE-CGS Network. The PE-CGS Network Steering Committee will be composed of one representative (contact PD/PI or other designated senior level investigator) from each PE-CGS awardee, i.e., from the PE-CGS U2C Research Centers and the PE-CGS U24 Coordinating Center who will have one vote each and a Project Scientist, who will have one vote for NCI.

If needed, other NIH staff members may also participate in PE-CGS Network Steering Committee meetings as non-voting members.

Two PD(s)/PI(s), representing two different PE-CGS U2C Research Centers, will be selected to serve as chairpersons of the PE-CGS Network Steering Committee starting at the first meeting of the PE-CGS Network Steering Committee following award issuance. All PE-CGS Network Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The PE-CGS Network Steering Committee will meet quarterly by videoconference and in-person at the PE-CGS annual network meeting, annual participant meeting, and as needed.

The PE-CGS Network Steering Committee will:

• Identify scientific and policy issues that can benefit by being addressed at the Network level and develop recommendations to NIH/NCI Program Officials for addressing such issues.
• Review progress of the PE-CGS Network toward meeting the overall Network goals.
• Receive input and guidance from the PE-CGS Network External Advisory Panel.
• Serve as a venue for consideration of ethical and psychosocial implications of returning genomic data results to participants.
• Ensure that all PE-CGS members utilize the resources developed by the PE-CGS U24 Coordinating Center.
• Discuss and prioritize the collaborative projects to be supported by the restricted "PE-CGS Collaborative Project" funds within each Research Center.
• Ensure that the Network takes advantage of existing NCI and NIH resources and programs.
• Establish, as necessary, subcommittees or working groups to ensure progress by tackling common issues for the individual Research Centers and the Network.

The Steering Committee may form sub-committees as needed, including the External Advisory Panel (see below).

PE-CGS Network External Advisory Panel. An External Advisory Panel (EAP) will be convened as a sub-committee to the PE-CGS Steering Committee. EAP will evaluate the progress of the PE-CGS Network and advise the Steering Committee and PE-CGC awardees regarding the scientific directions of the program. The panel will be logistically supported by the PE-CGS U24 Coordinating Center.

The PE-CGS Network EAP will be composed of nine individuals (selected by the PE-CGS Network Steering Committee), including established scientific leaders in oncological sciences, individuals with a history of cancer diagnosis, cancer advocates, and other stakeholders with relevant expertise. If needed, EAP membership may be enlarged permanently or on an ad hoc basis. The EAP will meet at least once a year, either in person with the Steering Committee meeting or by telephone conference.

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 RPPR, 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, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Leah E. Mechanic, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-6847
Email: NCI_PE-CGS@mail.nih.gov

Elizabeth M. Gillanders, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6764
Email: NCI_PE-CGS@mail.nih.gov

Wen-Ying Sylvia Chou, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-6954
Email: NCI_PE-CGS@mail.nih.gov

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

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@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.