Part 1. Overview Information

Key Dates

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 toall 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. Applicationsthat do not comply with these instructions may be delayed or not accepted for review,

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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)

Local 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)

Federal Governments

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Applicant organizations

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

• 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.
  • 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.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
  • Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.

• eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; 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 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

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.

Letter of Intent

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 for T-PDTCs should be sent to:

Jeffrey A. Moscow, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6101
Email:[email protected]

The letter of intent for D-PDTCs should be sent to:

Tiffany Wallace, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5114
Email:[email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

• Overall: required
• Administrative Core: required
• PDX Core: required
• Pilot Projects and Trans-Network Activities Core: required
• Bioinformatics Core: required
• Shared Resources Core: optional, maximum 1 allowed
• Research Projects: 2 required, maximum 3 allowed

Overall Component

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.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project Summary/Abstract: Provide overall goals/abstract/summary for the entire Center application.

Project Narrative: In the "Project Narrative", it is encouraged that the relevance of the Center’s research to public health should be stated in lay language.

Facilities and Other Resources:

In addition to standard items for this attachment, describe in detail the animal facility and relevant veterinary resources available. At a minimum, provide details on the following aspects:

• Facilities that will house immuno-incompetent animals, including all key technical parameters (such as available equipment, facility access design, and access control).
• Pathogen surveillance practices (animal pathogens as well as human pathogens), including specific pathogen types tested, the methods used for pathogen screening, screening frequency, etc. PDX models positive for the following human pathogens should be excluded: Human immunodeficiency virus 1 or 2, Hepatitis virus B, and Hepatitis virus C.
• Facilities housing PDXs planned for deposit to the PDMR-FNLCR or for sharing within the network should be negative for major pathogens including, but not limited to: Corynebacterium bovis, mouse norovirus (MNV), Lactic dehydrogenase-elevating virus (LDHV/LDEV), and mouse kidney parvovirus (MKPV). If some murine pathogens are endemic in your population, please consult with the PDMR-FNLCR to determine if the pathogen is allowable for model sharing.
• Summary of key standard operating procedures for the facility, including (but not limited to):
  • the types of xenograft procedures that the facility is capable of doing (e.g., orthotopic vs. subcutaneous);
  • systems for tracking tumor size and animal body weight;
  • procedures for review and approval of animal studies at the applicant’s Institutional Animal Care and Use Committee; and
  • procedures for harvesting tumor samples for cryopreservation and analyses.

Facilities housing PDXs planned for deposit to the PDMR-FNLCR or for sharing within the network must be negative for major pathogens including but not limited to: Corynebacterium bovis, mouse norovirus (MNV), Lactic dehydrogenase-elevating virus (LDHV/LDEV), and mouse kidney parvovirus (MKPV). If some murine pathogens are endemic in your population, please consult with the PDMR-FNLCR to determine if the pathogen is allowable for model sharing.

Project/Performance Site Locations (Overall)

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.

Research and Related Senior/Key Person Profile (Overall)

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

Investigators should include experience in PDX development (both orthotopic and subcutaneous), characterization of large-scale PDX collections, and in vitro models derived from PDX. Investigators should provide evidence of experience in testing drug combinations in PDX models as well as administration of drug by oral, intravenous (IV), and intraperitoneal (IP) methods to identify characteristics associated with therapeutic response to guide clinical development of anticancer agents.

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.

Budget (Overall)

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.

PHS 398 Research Plan (Overall)

Specific Aims: Outline the specific aims for the proposed Center.

Research Strategy: The research strategy should provide an overview of the testing of novel concepts and approaches that will provide preclinical evidence to guide the clinical development of promising new anticancer agents, and NCI-IND agents in particular, alone and in combination, using large-scale PDX collections and in in vitro models derived from PDXs. It is expected that strategies will identify molecular and other tumor characteristics that are associated with the therapeutic response.

Provide an overview of the proposed PDTC. Address all the specific aspects indicated below using the sub-sections as defined:

Sub-section A) PDTC Framework and Effort Integration. Describe the overarching organizational framework and vision of the proposed PDTC, its scientific focus, strengths, and leadership in the research field. Describe how the Center and the investigators team will collectively support the overarching goal of the Center, outlining multi-disciplinary and multi-institutional collaborations, as applicable.

Sub-section B) Research Team. Summarize the major collective strength of the research team in the proposed area of research. Without repeating information from individual biosketches, explain how the specific expertise of team members (e.g., cancer biology, genomics, molecular medicine, computational biology, bioinformatics, others) will be used to advance the proposed research program. Describe the environments (e.g., academic or other research) of the research team members and how they will support the mission of the proposed PDTC.

Sub-section C) Overview of Research Projects. Identify the overall focus of the PDTC research program. Outline the rationale for the proposed research projects, and reasons for their inclusion. Identify which of the scientific areas listed in Section I, under "Possible Research Areas" are addressed by two required projects. If a third research project is proposed, explain how it connects to the other two projects and the overall scientific theme of the proposed PDTC. Highlight the innovative aspects of all the proposed projects, as applicable.

D-PDTCs should provide evidence detailing sources of, and access to, racial/ethnically diverse cancer patients for the development of PDX models. A description on how these PDX models will be used to advance the understanding of potential therapeutic outcome disparities should be addressed.

T-PDTCs should address the overall strategy for testing novel drug combinations in large-scale PDX collections and in vitro PDX derived models to identify characteristics associated with therapeutic response.

Sub-section D) Translational Potential. Explain the translational potential of the proposed research on the responses to various treatments in PDX models of tumors with specific molecular characteristics. Explain particularly how the outcomes of the proposed research can be clinically validated, including the cancer center(s) or cancer clinical trial network(s) that would conduct the trial, the potential sources of funding for the trial, and how they may be useful clinically to help assign specific cancer therapies to only those patients who would be likely to benefit from them. Outline your overall foresight (beyond the scope of the PDTC award) on how PDX models can contribute to the ultimate clinical implementation of cancer precision medicine.

Letters of Support: All letters of support relevant to the overall application should be included here. Include a letter of support from an institution official endorsing the proposed PDTC and describing available institutional resources to support the Center’s research. Include letters from investigators who will serve as consultants or collaborators but with no measurable efforts.

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.

The following modifications apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• A Resource Sharing Plan should be provided only under the Overall component but it should cover all the activities proposed for the PDTC.
• Specimen Sharing: The plan should explain how the PDTC will share biospecimens and related information with other PDXNet investigators and PDMR-FNLCR pursuant to the terms of an informed consent. PDXNet investigators will be expected to share PDX models used in PDX trials with PDMR-FNLCR (and required to share PDX models that will be fully developed under the PDTC award). The plan should explain how the PDTC would structure an informed consent document with considerations for the wider sharing of data and specimens collected under a PDXNet award. The plan should include how the PDTC would provide information about the availability of PDX biospecimens at their institutions as well as associated clinical/demographic information to the patient registry-virtual biorepository created and maintained by the PDXNet Data Commons and Coordinating Center, consistent with achieving goals of the program.

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.

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application in ASSIST, use Component Type ‘Admin Core.’

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Title: Descriptive Title of Applicant's Project (use "Administrative Core")
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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.

Project /Performance Site Location(s) (Administrative Core)

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.

Research & Related Senior/Key Person Profile (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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 contact PD/PI of the PDXNet Research Center should serve as the Administrative Core Leader.

Budget (Administrative Core)

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

PD/PI Effort Commitment. Any PD/PI (whether designated as contact or not) must commit a minimum of 1.2 person-months effort per year to the award. This commitment cannot be reduced in later years of the award. Note that this is a minimum effort level that should be increased as appropriate to meet the needs of the work.

The budget should account for the efforts of other Core personnel (e.g., Core administrator) and a statistician.

The budget should include travel funds for the PD(s)/PI(s) and other senior investigators (up to four people) to attend the annual PDXNet Steering Committee meeting and participate in other network-related activities.

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.

PHS 398 Research Plan (Administrative Core)

Specific Aims: List the main goals for the Administrative Core.

Research Strategy:

Describe the anticipated roles of the Administrative Core. Address the specific aspects indicated below using the sub-sections as defined:

Sub-section A. Core Structure. Outline the organization and function of the Administrative Core. Describe the plans for coordination and communication with the PDCCC and NCI scientific staff.

Sub-section B. Leadership and Center Organization. Outline the organization of the leadership structure and overall Center structure (provide respective organizational diagrams). Describe the lines of responsibility.

Letters of Support: Include letters of support as appropriate.

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

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

PHS Human Subjects and Clinical Trials Information (Administrative Core)

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.

PDX Core

When preparing your application in ASSIST, use Component Type ‘Core.’

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

SF424 (R&R) Cover (PDX Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (PDX Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (PDX Core)

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.

Project /Performance Site Location(s) (PDX Core)

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.

Research & Related Senior/Key Person Profile (PDX Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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. It is expected that the Core will include substantial commitment of a Doctor(s) of Veterinary Medicine (DVM) and other highly qualified investigators.
• 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.
• Include experience with trials of agents and agent combinations and drug administration utilizing PDX models

Budget (PDX Core)

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

In the budget include (showing appropriate break down in Budget Justification):

• Personnel costs for the DVM-level staff member(s) and other skilled animal technical staff (for individuals who are not Key Persons) --explain briefly their roles and skills under Budget justification;
• The costs for obtaining and maintaining immunocompromised mice for the research plans; and
• The costs involved in PDX collection, storage, and quality control characterization.

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.

PHS 398 Research Plan (PDX Core)

Specific Aims: Describe the goals of the PDX Core.

Research Strategy:

Address the following aspects using the sub-sections as defined:

Sub-section A) Outline of the Core.

• Explain the overall capabilities of the PDX Core, e.g., in terms of the scale of operation, types of xenograft procedures used, types of drug testing conducted, collective skills/expertise (without repeating information in individual biosketches but including essential skills provided by individuals who are not covered by biosketches), and other relevant aspects;
• Outline plans to conduct comprehensive surveillance for pathogens to ensure facilities that are free of pathogens (including viral, bacterial, fungal, and parasitic agents) that are commonly regarded as unacceptable for such facilities (if the facility has allowable murine pathogens, please provide a list);
• Since Corynebacterium bovis is not part of most standard pathogen screens, please provide a statement regarding facility status of this pathogen;
• Explain any other steps planned to ensure that PDX models to be shared as a key feature of PDXNet are free of rodent pathogens;
• Describe PDX screening practices for human pathogens (such as HIV); and
• Describe other current approaches and plans for quality assurance/quality control of the Core operations and procedures.

Sub-section B) Core Collections.

• Describe the collections of PDX models and associated data at all the participating sites in the PDTC;
• Indicate whether the specimens are available for collaborative research studies with PDXNet as well as outside investigators;
• Describe any unique human cell lines/organoid collections available at the Center to support PDXNet research; and
• Describe PDX quality control procedures, such as steps taken to compare each passage generation to the original tumor and iterative short tandem repeat (STR) validation.

Sub-section C) Support for the Center Projects and PDXNet activities.

• Describe the role of the Core in facilitating the projects of the PDTC as well as possible contributions to collaborations with other PDTCs and non-Network investigators; and
• Describe how this Core will share and accept models from other PDTCs and the PDMR-FNLCR to allow cross-validation of experimental results and to enhance the diversity of tumor models among the PDTCs.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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

PHS Human Subjects and Clinical Trials Information (PDX Core)

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.

Pilot Projects and Trans-Network Activities Core

When preparing your application in ASSIST, use Component Type ‘Core.’

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

SF424 (R&R) Cover (Pilot Projects and Trans-Network Activities Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project (Use "Pilot Projects and Trans-Network Activities Core")
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Pilot Projects and Trans-Network Activities Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Pilot Projects and Trans-Network Activities Core)

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.

Project /Performance Site Location(s) (Pilot Projects and Trans-Network Activities Core)

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.

Research & Related Senior/Key Person Profile (Pilot Projects and Trans-Network Activities Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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.

Budget (Pilot Projects and Trans-Network Activities Core)

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

The budget request should account for the efforts of the Core Leader and other Key Persons and staff.

The budget should include restricted funds for pilot studies in the amount of $100,000 in direct costs per year, starting in year 2 of the project period. The funds include $50,000 in direct costs per year for within Center pilot studies and $50,000 in direct costs per year for Cross-PDXNet pilot studies. The release of these restricted pilot funds will be recommended to the PD/PI by the PDXNet Steering Committee and approved by NCI scientific staff, respectively. These amounts should be presented in the Other Expenses category under the heading “Restricted Pilot Project Funds.”

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.

PHS 398 Research Plan (Pilot Projects and Trans-Network Activities Core)

Specific Aims: Outline the main goals for the Core.

Research Strategy:

Describe the specific aspects indicated below using the sub-sections as defined:

Sub-section A. Pilot Studies Development and Evaluation. Outline the Research Center's overarching vision for the development of Pilot Projects and cross-PDXNet Projects. Pilot projects may serve, for example, as a mechanism to develop methods of experimental validation and reproducibility assessments across PDTCs. Outline the mechanisms that will be employed by the Core for soliciting, reviewing, prioritizing, and monitoring these projects. Include key scientific capabilities which the applicant Center can provide to support such projects. (NOTE: As specific Pilot Projects or cross-PDXNet Projects will be developed and selected post-award, specific projects should NOT be listed in the application.)

Sub-section B. Collaboration with non-PDXNet Investigators. Outline the PDTC's plans to enhance collaboration with non-PDXNet investigators in specific pilot studies. Outline the Center's vision for any other activities that could have a synergistic effect on the outcomes of the PDXNet Program.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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

PHS Human Subjects and Clinical Trials Information (Pilot Projects and Trans-Network Activities Core)

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.

Bioinformatics Core

When preparing your application in ASSIST, use Component Type ‘Core.’

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

SF424 (R&R) Cover (Bioinformatics Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Bioinformatics Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Bioinformatics Core)

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.

Project /Performance Site Location(s) (Bioinformatics Core)

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.

Research & Related Senior/Key Person Profile (Bioinformatics Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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.

Budget (Bioinformatics Core)

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

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.

PHS 398 Research Plan (Bioinformatics Core)

Specific Aims: Describe the goals of Bioinformatics Core.

Research Strategy:

Describe the specific aspects indicated below using the sub-sections as defined:

Subsection A. Capabilities

Describe how the Bioinformatics Core has the capacity to support study designs and data analysis for trials within the PDTC and, when needed, across the PDTCs, and in conjunction with the data management personnel of the PDCCC. Examples of relevant capabilities may include, but are not limited to:

• Established statistical and computational methodologies for interpretation of the complex data generated from molecular characterization of PDX models and from PDX responses to agent and agent combinations
• Systems to track progress of PDX trials (available or possible to design and implement)

Subsection B. Approaches

Describe how the Bioinformatics Core can develop novel approaches to study designs and data analysis for trials within the PDTC and, when needed, across the PDTCs, and in conjunction with the data management personnel of the PDCCC. Examples of relevant capabilities may include, but are not limited to:

• Approaches to create algorithms for different data types including Omics data (e.g., genomics, RNAseq, etc.)
• Developing approaches to integrate PDX molecular characteristics with PDX response data to generate both hypothesis-testing preclinical studies and proposals for human clinical trials.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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

PHS Human Subjects and Clinical Trials Information (Bioinformatics Core)

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.

Shared Resources Core

When preparing your application in ASSIST, use Component Type ‘Core.’

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

SF424 (R&R) Cover (Shared Resources Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Shared Resources Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Shared Resources Core)

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.

Project /Performance Site Location(s) (Shared Resources Core)

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.

Research & Related Senior/Key Person Profile (Shared Resources Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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.

Budget (Shared Resources Core)

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

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.

PHS 398 Research Plan (Shared Resources Core)

Specific Aims: Describe the goals of the Shared Resource Core. Indicate which specific Research Projects will be served by this Core.

Research Strategy: Justify why the Shared Resource Core is needed and how it will facilitate PDTC research projects. (The Shared Resource Core must support at least two PDTC Research Projects.) Any additional services, support, and/or resources to be provided to other Research Center components (if applicable) should be clearly defined.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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

PHS Human Subjects and Clinical Trials Information (Shared Resources Core)

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.

Research Project

When preparing your application in ASSIST, use Component Type "Project".

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project (Starting with "Research Project 1" or "Research Project 2" or "Research Project 3)
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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.

Project /Performance Site Location(s) (Research Project)

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.

Research & Related Senior/Key Person Profile (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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.

Budget (Research Project)

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

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.

PHS 398 Research Plan (Research Project)

Specific Aims: Outline the Specific Aims of the project.

Research Strategy: Applicants should use the standard structure of the Research Strategy section (i.e., sub-sections Significance, Innovation, and Approach) defined in the SF424 Application Guide with additional guidance as defined below.

Statement of Research Area(s) Relevance.If a given Research Project is one of two required projects, include at the beginning of Research Strategy a statement identifying which of the possible research areas (listed in Section I) is/are being addressed by a given project. For an optional research project, indicate how that project connects to research area(s) of the required projects.

The research plan should test novel concepts and approaches that will provide preclinical evidence to guide the clinical development of promising new anticancer agents, and NCI-IND agents in particular, alone and in combination, using large-scale PDX collections and in in vitro models derived from PDXs. The plan should also include strategies that can identify molecular and other tumor characteristics that are associated with the therapeutic response.

If applying for the D-PDTC, state clearly whether or not this project is the required project addressing disparities that exist for therapeutic outcomes, using a comparative research design between at least two racial/ethnic populations. The research plan for D-PDTCs should also describe how it will contribute to the racial/ethnic diversity represented in the overall PDXNet effort and how it will fill identified resource gaps in the PDMR collection related to representation of patient-derived cancer models from patients with racially diverse backgrounds. D-PDTCs should also provide evidence detailing the source of and access to racial/ethnically diverse cancer patients for the development of PDX models A description on how these PDX models will be used to advance the understanding of potential therapeutic outcome disparities should be addressed.

Emphasis should be placed on explaining why the proposed concepts and approaches are innovative within the context of related research and how the expected outcomes will contribute to clinical trial development and advance cancer precision medicine. In appropriate sub-sections, address the integration in and contribution of the research project to the overall Research Center program. Explain why a given project is essential for achieving the Center's overarching goals.

Under the Approach subsection, clearly describe the number of PDX models that will be used per project, noting that the goal is to select from and to use a large number of unique PDX models per project to better understand the molecular determinants of therapeutic response to a proposed therapeutic combination. Provide characteristics of these models, including their sources/availability (whether previously established or to be developed), distribution of cancer types, self-reported racial/ethnic background or genetic ancestry, etc. Describe how PDX drug response will be related to PDX characteristics.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component of the application.

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

PHS Human Subjects and Clinical Trials Information (Research Project)

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.

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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 fieldof the Senior/Key Person Profile form. 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 unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Post Submission Materials

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.

Section V. Application Review Information

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.

For this FOA, note the following:

The focus of this initiative is to use patient-derived xenografts (PDXs) and in vitro models derived from PDXs to develop novel anticancer therapies in tumors with specific characteristics to advance the concept of cancer precision medicine. This requires large and diverse PDX collections with associated advanced molecular characterization, and in vivo and in vitro drug-response studies conducted in the context of mechanistic, hypothesis-driven research. The association of awardees in a collaborative network is intended to foster development of PDX models, data sharing methods, and standardization of procedures related to PDX therapeutic testing that can be shared with wider research community.

Scoring: Reviewers will provide an overall impact score for the entire PDTC application. In addition, reviewers will also provide individual "criterion scores" for the Overall application but not for the other components.

All other components of the Center [i.e., Administrative Core, Research Project, PDX Core, Pilot Projects and Trans-Network Activities Core, Bioinformatics Core, and optional Shared Resource Core] will be evaluated but each will receive only one overall adjectival rating.

For the evaluation of the PDTC application, the Research Projects will be emphasized as the scientific base of each Center, with additional components enhancing and integrating the overall research/outreach program.

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

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

Significance

Does the project 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 project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

How well does the proposed PDTC use patient-derived models to address an important therapeutic question or a critical barrier to producing clinical benefits of anticancer therapies? How well does the information in the application support a strong scientific premise for the project?

For T-PDTCs: What is the likelihood that the PDTC research, as proposed, will help advance cancer precision medicine? How well will the proposed concepts and approaches help provide preclinical evidence to guide the clinical development of new promising anticancer agents, and NCI-IND agents in particular? How well does the research plan test novel drug combinations in large-scale PDX collections and in in vitro models derived from PDXs, in a manner that will help identify characteristics that are associated with the therapeutic response? How well will the proposed PDTC meaningfully contribute PDX models and associated data to the PDMR that fill identified resource gaps to share with the larger research community?

For D-PDTCs: What is the likelihood that the D-PDTC research, as proposed, will help advance cancer precision medicine? What is the likelihood that the D-PDTC research, as proposed, will help advance cancer disparities research? How well will the proposed concepts and approaches help provide preclinical evidence to guide the clinical development of new promising anticancer agents, and NCI-IND agents in particular? How well will the proposed D-PDTC meaningfully contribute to and facilitate the PDMR goals of developing PDX models and associated data to share with the larger research community? How well will the proposed D-PDTC contribute to the racial/ethnic diversity represented in the overall PDXNet?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:

How well does their evidence show the backgrounds, expertise, and commitments of the PD(s)/PI(s) and other key persons are adequate for the proposed scope of activities and in line with the overall goals of the PDXNet? How well have the PDTC investigators demonstrated expertise in the development and characterization of large-scale PDX collections and in in vitro models derived from PDXs? How well does the information in the application show the investigators demonstrate expertise in PDX development, including development of both orthotopic and subcutaneous PDX models? How well does the information in the application show that the investigators demonstrate expertise in conducting trials of agent and agent combinations in groups of PDXs, including administration of drug by oral, intravenous (IV), and intraperitoneal (IP) methods at human-relevant dosing preclinical drug testing on PDX models?

Innovation

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

Specific to this FOA:

How well does the proposed PDTC employ novel concepts, approaches, and/or methods to use PDX models, and in vitro models derived from PDXs, for preclinical testing of cancer therapies? How novel are the proposed PDTC strategies for integrating and cross-validating molecular characterization and pre-clinical therapeutic data from diverse datasets? How are the PDTC's goals original and novel?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the 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?

Specific to this FOA:

How are the investigator’s plans to address relevant biological and technical variables inherent in early-passage PDX models across multiple sites adequate and appropriate? How adequate and appropriate are the projects testing multiple combinations of anticancer agents, including NCI-IND agents, in large-scale collections of patient-derived models, and a strategy to correlate molecular characterization of these models with drug response data? If patient-derived models other than PDX are proposed, how is their use appropriate and well-justified in the context of the main thrust of effort of using in vivo PDX models for preclinical evidence development? How well does the research plan demonstrate how PDX models will be used to develop the rationale for novel ETCTN clinical trials using combinations of agents to treat molecularly-defined tumors? If non-NCI-IND agents are the focus of the research plan, how feasible is their plan for subsequent clinical validation of the research results?

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

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA:

How well will the proposed PDTC be able to make consistently rigorous and meaningful contributions to the entire PDXNet and the participating institutions (in particular PDMR-FNLCR) e.g., in terms of contributing innovative PDX models that are well-characterized and rigorously screened for pathogens before sharing? How well will the proposed PDTC take advantage of the infrastructure for PDXNet and existing resources at the participating institutions, and in particular PDMR-FNLCR? For D-PDTC's, how appropriate is the institution’s access to racial/ethnic diverse cancer patients for the development of PDX models?

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

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of 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.

Vertebrate Animals

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.

Biohazards

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

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the current funding period.

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

Scored Review Criteria - Cores and Research Project

For each of the Center's components below (i.e., Administrative Core, Research Projects, PDX Core, Pilot Projects and Trans Network Activities Core, Bioinformatics Core, and optional Shared Resources Core), reviewers will provide an overall adjectival rating to reflect their assessment of the likelihood for the component to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria. Reviewers will consider the following aspects while determining scientific and technical merit of each component. Criterion scores will not be provided for the Cores and the Research Project.

Review Criteria - Administrative Core

As described for the Administrative Core, how adequate is the managerial and collaborative capabilities of the proposed leadership? How appropriate are the leadership structure and activities of the proposed PDTC in terms of facilitating: achievement of the overall goals of the PDTC; integration of multiple institutions participating in a given PDTC (as applicable); and collaboration in cross-PDXNet activities?

Review Criteria - PDX Core

How well is this Core integrated in the proposed PDTC? How well will the Core allow the proposed PDTC, as a whole, to be responsive to the scientific challenge of validating and reproducing PDX research results? How adequate are the veterinary resources, animal holding facilities and quality control procedures for high-quality PDX therapeutic trial testing and for collaborative PDX research projects? How well will the facility’s infection control procedures and pathogen surveillance and screening practices minimize the risk of contamination of facilities that receive shared PDX models? How well does the Center outline its intent to collaborate and share specimens and cell models within the PDTC and across the PDXNet program as appropriate and consistent with achieving the goals of the program?

Specific for D-PDTCs: How well does the PDX core’s record of achievement support their ability to establish PDX models from racially and ethnically minority populations?

Review Criteria - Pilot Projects and Trans Network Activities Core

How well-designed and feasible are the overall vision and specific plans for pilot projects? How adequate and sufficient is the attention given to planning for the participation in trans-network collaborations as well as potentially engaging non-PDXNet investigators?

Review Criteria - Bioinformatics Core

How well is this Core integrated in the proposed PDTC? How well does the Core provide expertise to interpret complex data generated from molecular characterization of PDX models and from PDX responses to agent and agent combinations? How well can it help develop approaches to create algorithms for different data types including omics data? How well can it assist in the development and implementation of systems to track progress of PDX trials?

Review Criteria - Optional Shared Resources Core (if applicable)

How well-matched is the proposed Shared Resources Core to the needs of the overall Research Center? How well will the proposed Core meaningfully enhance the Center's research program? How essential are the services of the Shared Resources Core to the goals of more than one Research Project? How adequate and appropriate are the qualifications, experience, and effort commitment of the Shared Resources Core Director(s) and other key personnel for providing the proposed facilities or services? How well will the proposed Shared Resources Core provide cost-effective services to the Research Center, prevent duplication, and/or increase efficiency?

Review Criteria - Research Projects

Significance

How well does the project address an important problem or a critical barrier in preclinical testing of new anticancer agents? How strong is the scientific premise for the project? If the aims of the project are achieved, how much will scientific knowledge, technical capability, and/or clinical practice be improved? How much will successful completion of the aims change the clinical approaches to matching treatments with molecular characteristics of individual patients' tumors? How well is this project connected to other project(s) proposed for the Center?

Investigator(s)

How well suited are the Project Lead, collaborators, and other researchers to the project? If the project is collaborative, how complementary and well-integrated are the investigators’ expertise?

Innovation

How appropriate and feasible are the proposed novel methods for testing anticancer agents in PDX models and/or innovative pre-PDX screening?

Approach

How well-reasoned and appropriate are the overall strategy, methodology, and analyses to accomplish the specific aims of the project? How well do the investigators’ strategies ensure a robust and unbiased approach, as appropriate for the work proposed? How practicable and adequate are the potential problems, alternative strategies, and benchmarks for success presented? How sufficient are quality assurance and quality control measures to ensure that PDX models used for studies are free from microbiological contaminations? How well have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Environment

How well will the scientific environment in which the work will be done contribute to the probability of success? How adequate are the institutional support, equipment and other physical resources available to the investigators for the project proposed? How beneficial to the project are the unique features of the PDTC environment including the Cores and Projects?

Additional Review Criteria - Cores and Research Project

As applicable for the Cores and Projects proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall adjectival rating, 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 project 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)?

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of 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.

Vertebrate Animals

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

Biohazards

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

Additional Review Considerations - Cores and Research Project

As applicable for the Cores and Projects 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 adjectival rating.

Applications from Foreign Organizations

Not applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources

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.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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 will receive a written critique.

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Programmatic priority may be given to applications centered on types of agents that are regarded by the NCI as clinically most promising, including specifically those in the NCI-IND portfolio.

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in theNIH 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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Prior Approval of Pilot Projects

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 comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• 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: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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.

Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution's specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.

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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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, and other HHS, PHS, and NIH grant administration policies.

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

An NCI Program Director acting as the Program Official will be responsible for the normal programmatic stewardship of the award and will be named in the award notice.

The PD(s)/PI(s) will have the following primary responsibilities

• Determine the PDTC’s directions, coordinate research approaches and procedures, and oversee the analyses and interpretation of research data;
• Oversee the timely release and sharing of specimens and data according to the NCI approved resource sharing plans;
• Participate in the development and evaluation of pilot projects, cross-PDXNet Projects, and cross-PDXNet activities that will cross-test novel projects;
• Participate in the annual PDXNet Steering Committee meeting, and periodic conference calls organized by the PDXNet Data Commons and Coordinating Center;
• Cooperate with NCI Project Scientists in the program evaluation process;
• Accept and implement all scientific and practical decisions approved by the PDXNet Steering Committee to the extent consistent with applicable grant regulations; and
• Take advantage of collaboration with other NCI and NIH initiatives and programs, as appropriate for advancing the Center research and the PDXNet program.
• The following additional responsibilities will also apply for each PDTC awardee:
• Each PDTC and the entire PDXNet program will be subject to periodic performance evaluation (coordinated by the PDXNet Steering Committee Chair) and external evaluation (coordinated by the NCI). PDXNet Awardees will be expected to participate in these evaluations;
• 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;
• All institutions/organizations participating in a given Research Center will be expected to share with the PDXNet program knowledge, specimens, data, research materials, and any other resources necessary and relevant to the PDTC award, consistent with achieving the goals of the program;
• Participate in the evaluation of applications from outside investigators for access to resources in the PDXNet centers, and collaborate with funded investigators when appropriate;
• Each PDTC is expected to operate under SOPs developed by the PDXNet in collaboration with PDMR-FNLCR to ensure reproducibility and comparability of data between consortium centers. SOPs will include methods for the development of PDX models and for testing anticancer agents in these models;
• Each PDTC is expected to provide all new PDX models developed under the PDTC award to PDMR-FNLCR without encumbrance;
• PDs/PIs are expected to conform with all human subjects research guidelines, including ensuring that consent forms allow for PDX model development and sharing of data or indicate willingness to add language into existing protocols for research specimen collection; and
• The applicants are expected to accept (to the extent consistent with grants regulations) the overall governance of the program, and program policies including, as applicable, guidelines, recommendations and procedures on: the use of common protocols, publication of study results, collaborative procedures, confidentiality, and data sharing plans to be developed by the PDXNet in collaboration with NCI.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The designated NCI Program staff members will have substantial involvement as Project Scientists in the awards under this FOA. The specific roles of the substantially involved NCI staff members include the following activities:

• Serve as the NCI lead Project Scientists and voting members (with one vote collectively) of the PDXNet Steering Committee;
• Assist in avoiding unwarranted duplications of effort across the PDXNet program;
• Help coordinate collaborative research efforts that involve multiple PDTCs;
• Monitor the operations of the PDXNet PDTCs and make recommendations on overall project directions and allocations of funds. NCI staff will perform periodic (at least annual) site visits to the PDTCs to review scientific and administrative progress and to ascertain that SOPs and other agreed upon procedures are implemented and being followed;
• Review the progress of individual PDTCs and specific activities shared among the Research Centers and Coordinating Center;
• Participate in the development and evaluation of cross-PDXNet Projects;
• Co-organize and participate in the annual PDXNet Steering Committee meeting. Participate as Collaborators of the PDXNet investigators in some shared activities, if appropriate;
• Assist the PDXNet awardees as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes and effectively leverage existing NIH/NCI resources and infrastructures;
• Provide clinical background information on the clinical development of investigational agents to guide the development of PDX trials;
• Provide an NCI staff liaison between PDXNet investigators and investigators in the ETCTN to facilitate translation of PDXNet research results into clinical trials;
• NCI staff at FNLCR will receive, analyze and characterize PDX models received from PDX Network investigators;
• NCI staff at FNLCR will help to coordinate the development of SOPs to be used by PDX Network investigators; and
• Evaluate the adherence of PDXNet awardees to approved resource sharing plans.

Additionally, an NCI Program Director acting as the Program Official and a Science Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibilities include the following:
The PDXNet Steering Committee will serve as the main governing board of the PDXNet program.
The committee will consist of the following voting members:

• The PD(s)PI(s) of each awarded PDTC who will have one vote for each PDTC, regardless of the number of PDs/PIs designated;
• The PD/PI of the PDCCC and a designated senior investigator who will collectively have one vote;
• The NCI/PDXNet Project Scientist(s) who will collectively have one vote representing PDXNet/NCI; and
• The PDMR-FNLCR liaison who will have one vote.

The PDXNet Steering Committee will meet at least one time per year in a face-to-face meeting. A chair of the PDXNet Steering Committee will be selected at the first meeting to coordinate the committee's operation. The PDXNet Steering Committee chair will meet by teleconference with NCI Project Scientists as needed to address program issues.

Additional non-voting members who can serve in an advisory capacity may be added to the PDXNet Steering Committee as needed by a decision of the existing voting committee members. These additional non-voting members may include other NCI and NIH Program Staff members and/or Program Staff members from other Federal agencies.

The PDXNet Steering Committee will have the following primary responsibilities:

• The PDXNet Steering Committee will meet monthly to oversee the overall PDXNet program and review its research progress;
• Review the potential of shared support infrastructure(s) at individual PDTCs to serve the needs of other PDTCs and the entire program;
• Develop procedures for soliciting and evaluating concepts for pilot projects across the PDXNet as well as criteria for their prioritization and approval by the PDXNet Steering Committee;
• Ensure that the PDTCs and the PDCCC take advantage of existing NCI and NIH resources and programs;
• Make recommendation for termination of pilot projects that become unpromising or unproductive;
• Participate in the development of the agenda for an annual PDXNet meeting where PDXNet investigators present scientific progress and future plans to the PDXNet Steering Committee;
• Coordinate the PDXNet evaluation of applications from outside investigators for access to resources in PDXNet centers, and coordinate collaborate with funded investigators when appropriate;
• Establish advisory groups as necessary to ensure the progress of individual Research Centers as well as of the entire PDXNet program;
• Ensure that individual PDXNet members (i.e., PDTCs and PDCCC) accept and implement as appropriate actions (recommendations, directions, etc.) approved by the PDXNet Steering Committee; and
• The PDXNet Steering Committee will conduct performance evaluation of the PDTCs and the PDCCC. The purpose of this endeavor (to be coordinated by the PDXNet Steering Committee Chair) will be to monitor progress and provide feedback to individual PDTCs. Such feedback will facilitate optimization of various aspects of the program and implementation of corrective actions if needed. The overriding goal will focus on identifying approaches to translational research that could not be achieved by individual investigators working separately and, thereby, increasing the likelihood for significant scientific advances.

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, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

Progress reports should briefly describe status of pilot projects, including data and safety monitoring, and should notify NIH of serious adverse events and unanticipated problems.

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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 75and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Jeffrey A. Moscow, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6565
Email: [email protected]

Tiffany Wallace, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5114
Email:[email protected]

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

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.