Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title
PDX Data Commons and Coordinating Center (PDCCC) for the PDX Development and Trial Centers Research Network (PDXNet) (U24 Clinical Trial Not Allowed)
Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type
New
Related Notices
  • April 5, 2022 - Notice of Correction to RFA-CA-22-013, "PDX Data Commons and Coordinating Center (PDCCC) for the PDX Development and Trial Centers Research Network (PDXNet) (U24 Clinical Trial Not Allowed)" . See Notice NOT-CA-22-073
Funding Opportunity Announcement (FOA) Number
RFA-CA-22-013
Companion Funding Opportunity
RFA-CA-22-012 , U54 Specialized Center (Cooperative Agreements)
Assistance Listing Number(s)
93.396
Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to establish a PDXNet Data Commons and Coordinating Center (PDCCC). PDCCC will interact with and coordinate with the PDX (Patient-Derived Xenograft) Development and Trial Centers Research Network (PDXNet) comprised of five PDX Development and Trial Centers (PDTCs, to be supported by companion FOA, RFA-CA-22-012) in a collaborative network. The PDXNet is a National Cancer Institute (NCI) program established to coordinate collaborative, large-scale development and pre-clinical testing of targeted therapeutic agents in patient-derived models to advance the vision of cancer precision medicine. The goals for PDTCs include development of preclinical data in PDX models to translate into clinical trials; the strategic development of new PDX models to fill public resource gaps; and development of new methods and metrics for preclinical in vivo testing of single agents and drug combinations. The PDCCC will serve as the coordinating and data analysis center of the PDXNet. It is expected that the outcomes of PDXNet research will be particularly important for the prioritization of combinations of agents in the portfolio of NCI Investigational New Drugs (NCI-IND agents), which are evaluated clinically in the NCI’s Experimental Therapeutic Clinical Trials Network (ETCTN).

PDXNet will encompass up to five PDTCs (to be supported by a companion FOA, RFA-CA-22-012) and a single PDCCC (to be supported by this FOA). PDXNet will be supported by the NCI Patient-Derived Models Repository (PDMR) at the Frederick National Laboratory for Cancer Research (FNLCR). PDTCs and the PDCCC will be expected to collaborate with PDMR in several areas related to the goals of the program, including the development of optimized standardized procedures, and in sharing PDX models.

Key Dates

Posted Date
March 25, 2022
Open Date (Earliest Submission Date)
October 01, 2022
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 01, 2022 Not Applicable Not Applicable March 2023 May 2023 July 2023

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Funding Opportunity Announcement

Expiration Date
November 02, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) solicits applications for PDXNet Data Commons and Coordinating Center (PDCCC) that will interact with and coordinate with the PDX (Patient-Derived Xenograft) Development and Trial Centers Research Network (PDXNet) which will be comprised of up to five PDX Development and Trial Centers (PDTCs). The PDTCs will be supported by a companion FOA, RFA-CA-22-012. The PDTCs and the PDCCC will form a collaborative network.

The PDXNet is an NCI program that advances the use of patient-derived models (PDMs), with a focus on patient derived xenografts (PDXs) to develop new cancer therapies. PDXNet employs advanced molecular characterization of PDMs and PDXs to identify both active combinations of targeted agents, and the molecular characteristics of tumors most likely to respond to these combinations, for subsequent testing in early phase clinical trials.

Each PDTC will encompass a research program with PDX development and PDX drug response experience, and bioinformatics expertise. The PDCCC will help to organize these individual PDTCs into the coordinated PDXNet network, by facilitating network interactions and collaborations, establishing and maintaining bioinformatics and data analysis platforms, providing the mechanisms for sharing PDXNet data with the larger scienti?c community, and coordinating participation in cross-PDXNet pilot projects. PDXNet and the PDCCC will be expected to collaborate closely with the NCI Patient-Derived Models Repository (PDMR) at the Frederick National Laboratory for Cancer Research (FNLCR). Through these collaborative e?orts, PDXNet can accelerate the integration and translation of important research ?ndings generated from pre-clinical PDX models to bene?t cancer patients.

Key Terms for this FOA

  • Patient-derived xenografts: The term “patient-derived xenograft” or "PDX" refers to cancerous tissue from a patient's tumor that is implanted directly into an immunode?cient animal (usually mouse).
  • PDX trials: A "PDX trial" is a controlled experiment where drug and drug combinations are administered to mice bearing PDX’s, and where the outcome is the response of the tumor to the therapy. In a large-scale PDX trial, the molecular characterization of the PDX models is used to identify potential biomarkers of response to the regimen.
  • PDX development: The development of PDX models can include steps beginning with tumor cell acquisition from the patient up to and including the original implantation in the host through characterization of the tumor in successive passages. PDX development can include using PDX material for in vitro assays to improve the e?ciency of determining promising regimens for in vivo studies.
  • Clinical validation: PDX trials are expected to identify drug combinations that are active against molecularly- de?ned subsets of tumors. The clinical validation of PDX experimental results requires a human study where the patients’ tumor has the biomarker(s) that match those of the responsive PDX model(s), and where the drugs and schedule of administration closely match the PDX trial. The clinical study determines whether the PDX biomarkers actually assist in identifying patients who will bene?t from the PDX drug combination.

Background

The PDXNet is a network of centers of excellence that have developed PDX patient-derived models on a large scale and collaborate to perform in vivo drug-response studies with these models to address the challenges of cancer precision medicine. Beginning in FY17, PDXNet was formed as a Cancer Moonshot program through two FOAs. The network is currently comprised of four PDX Development and Trial Centers (PDTC’s) (RFA-CA-17-003) and one PDXNet Data Commons and Coordinating Center (PDCCC) (RFA-CA-17-004). In FY2018, the NCI Center to Reduce Cancer Health Disparities issued an RFA (RFA-CA-17-032) that added two additional PDTCs to PDXNet with the goal of developing more racially diverse PDX models and propose PDX research to better understand therapeutic outcome disparities. PDXNet functions as a network and uses a cooperative agreement award mechanism to both perform original research and to address NCI program priorities in collaborative efforts.

Use of PDX Models for Translational Cancer Research. PDX models represent an emerging platform for translational cancer research. When properly derived from original biospecimens and properly maintained, PDX models more accurately represent human cancers than established cancer cell lines. Therefore, testing anticancer agents in PDXs may be more accurate in predicting the response of patients' tumors to these agents in the clinic than traditional testing in established cell lines. Advances in genomic sequencing technology and bioinformatics make it possible to extensively characterize each PDX model. By combining advances in the establishment of PDX models and in the depth of molecular characterization, PDXs could be used to identify the optimal combination therapy for increasingly smaller groups of more precisely de?ned cancers (i.e., addressing the emerging goals of the precision cancer medicine).

As both the number of experimental anticancer agents and the number of recognized tumor sub-types grow larger, the paradigm of conducting Phase 1 studies followed by Phase 2 studies of each promising drug combination on each tumor subset becomes prohibitive, both in terms of cost and practicalities of patient accrual. Cancer precision medicine requires new e?ective ways to match the sub-types of patients' tumors (that can be precisely characterized at molecular levels) to available cancer therapeutic agents (which increasingly often act on speci?c molecular targets). PDX models have the potential to facilitate this matching as they can be used in multiple tumor models against multiple therapeutic drug combinations.

By using PDX’s in multiple ‘pre-clinical clinical trials’ that test numerous agent combinations against numerous extensively characterized human tumors, evidence-based guidance can be obtained on the most promising combinations to test in de?ned sub-populations of cancer patients. To realize this promise, research is needed on the optimal ways to integrate PDX drug response data with the vast molecular characterization data that are available for most PDX models. Such research, to optimally mimic human cancer heterogeneity, should use large- scale collections of PDX models to increase the likelihood that PDX-based predictions of clinical responses are re?ective of the complexities of individual patients' cancers.

Challenges of PDX Models. Most PDX models are currently being developed in many isolated programs in institutions across the country, creating an environment where there is little standardization of procedures or the possibility of validating and replicating results. These isolated PDX collections are not large enough to su?ciently re?ect the diversity of clinical tumors needed to provide the foundational evidence for clinical trials of drug combinations in molecularly-de?ned cancers. Therefore, there is a need for a coordinated and collaborative research e?ort for large-scale development of PDXs using standardized procedures and rigorous model validation approaches to advance the clinical development of new anticancer agents.

Overall Goals for the PDXNet

The primary goal for the PDXNet will be to develop appropriate PDX models and methods for preclinical testing of single agents and drug combinations. These models should allow the determination of the optimal treatments (single drugs or combinations) that should be tested in clinical trials in increasingly smaller, molecularly-de?ned subsets of tumors. The proposed PDCCC must be able to contribute meaningfully to the overall goal for the entire PDXNet and will be expected to directly address the challenge of precision cancer medicine – how to prioritize the clinical testing of many targeted agents in many tumor subtypes.

It is also the goal of the PDXNet to develop drug combinations in de?ned tumor subsets in a context that can feasibly lead to clinical validation of the experimental results. Therefore, this FOA has an emphasis on NCI-IND agents that are primarily used by the Experimental Therapeutics Clinical Trials Network (ETCTN). By focusing PDXNet trials on these agents, there is a ready-made path to clinical development should the PDXNet experiments provide clinical leads that merit exploration. When NCI-IND agents are included in drug combinations in the PDTC research plans, NCI will be able to provide the ETCTN clinical platform for testing and clinical validation of the pre- clinical research results of the PDTC investigators to determine if the PDXNet research results can be translated into clinical bene?t. Through the NCI Experimental Therapeutics (NExT) program, NCI’s Division of Cancer Treatment and Diagnosis (NCI/DCTD) has formed collaborations with pharmaceutical companies and academic medical centers to develop over sixty anticancer agents. These agents are brought into clinical trials through the ETCTN, a network of early phase clinical trial sites supported by a centralized clinical trial infrastructure that is devoted to the conduct of early clinical studies of NCI-IND agents.

Research to be conducted by PDXNet may include agents that are not under NCI-IND. However, since these agents will not have the ready-made path via the ETCTN to clinical development, they will require a clear and feasible strategy for the translation of PDX research results into novel clinical trials, so that the ultimate goals of the PDXNet can be ful?lled.

Role of Patient-Derived Models Repository at the FNLCR. Central to the function of the PDXNet is the role of the NCI PDMR-FNLCR. This facility is developing PDX models from samples obtained across the nation, with the goal of creating a large, genetically characterized PDX bank that will be shared with investigators to facilitate PDX research. PDTC investigators will be expected to deposit PDX models to be expanded by the PDMR-FNLCR so that these models can be shared with the wider research community. To facilitate collaborative interactions within the PDXNet, the PDMR-FNLCR sta? will help to coordinate the development of Standard Operating Procedures (SOPs) both for PDX development and PDX drug response testing in the network and will approve the SOPs to be used in PDXNet.

Key Requirements of the PDXNet Data Commons and Coordinating Center (PDCCC)

The proposed PDCCC must meet the following main attributes (for additional details on the requirements, please see Section IV. Application and Submission Information (//grants.nih.gov/grants/guide/rfa-?les/RFA-CA-22-013.html#_Section_IV._Application_1)):

  1. Overall Role. The PDCCC will have an important role in integrating the e?ort of individual PDTCs. The Coordinating Center should provide administrative and logistic support for the PDXNet program and be able to connect available resources as well as serve as the network data management center. The PDCCC will be expected to interact with the PDTCs and coordinate various trans-Network activities, e.g., to standardize (as appropriate and needed) approaches, procedures, data formats, etc., and/or to minimize resources/e?ort duplication.
  2. Leadership and Administration. The Coordinating Center must be able to provide close coordination of trans-network and trans-disciplinary research conducted by the PDTCs. This role will require strong leadership, scienti?c oversight, and managerial capacity to bring diverse teams together.
  3. Bioinformatics. The Coordinating Center must be able to provide bioinformatics and biostatistics expertise suitable for the analyses and integration of complex biological data from multiple experimental platforms and other sources, and to create and maintain a searchable database. The data to analyze will include: clinical data for cancer patients, whose tumors were used to derive individual PDX models, various molecular characterizations and other -omic data of PDX models, images and image analysis of PDX models, and PDX treatment response data collected at the PDTCs. It is expected that the PDCCC will serve a key role in PDXNet by integrating the ?ndings of individual PDTCs and distilling them into actionable recommendations for the design of speci?c clinical trials (which will ultimately be developed and conducted by other NCI-supporting programs interacting with PDXNet).

Governance of the PDXNet

The PDXNet (i.e., PDTCs and PDCCC) will be governed by the PDXNet Steering Committee. Details on the composition and functions of PDXNet Steering Committee are provided in Section VI.2, Administrative and National Policy Requirements, Cooperative Agreement Terms and Conditions.

Evaluation of the PDXNet Program

PDXNet awardees will be expected to participate in an external evaluation process that will be coordinated by the NCI Scienti?c sta?. This evaluation will largely be based on the overall progress towards achieving the scienti?c goals of the entire PDXNet Program.

Non-responsive Applications

Non-responsive applications include:

  • Applications that do not propose establishing and operating a centralized PDX-related data collection, management, analysis, and dissemination unit to support the entire PDXNet.
  • Applications that do not provide data informatics and computational resources required for hosting PDXNet collaborative projects
  • Applications that do not describe how PDXNet project management will be coordinated by staff with expertise in PDX science and informatics.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New
Renewal

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

NCI intends to fund one PDCCC award, corresponding to direct costs of $650,000 for fiscal year 2023.

Award Budget

Application budgets must reflect the actual needs of the proposed project but must not exceed $650,000 per year in direct costs.

Award Project Period

The total project period is 5 years.

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

Eligible Organizations

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 Government

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

Other

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

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. 

Required Registrations

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.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(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, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

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 should be sent to:

Jeffrey A. Moscow, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6565
Email: jeffrey.moscow@nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Facilities and Resources: Describe infrastructure to support the PDCCC, including speci?cally information technology systems, data storage systems, and capacities, etc.

SF424(R&R) Senior/Key Person Profile

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

Within the biosketch, include details about the investigator's experience in managing multi-institutional cancer research, with multi-disciplinary and/or multi-institutional programs, with preclinical cancer models, and in anti-cancer drug testing and/or drug development.

R&R Budget

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

The budget should include:

  • PD/PI E?ort Commitment: Any PD/PI (whether designated as contact or not) must commit a minimum of 1.2 person-months e?ort per year to the award. This commitment cannot be reduced in later years of the award. Note that this is a minimum e?ort level that should be increased as appropriate to meet the needs of the research project.
  • The budget request should account for the e?orts of the statistician, computer scientist and data collection in the PDCCC. There are no restrictions on these e?ort levels. The effort levels should be well justi?ed in the context of the PDCCC needs.
  • The budget request may include the costs of additional computational hardware, software and data storage upgrade costs, if necessary, to meet the needs of PDXNet. However, such upgrade items must be well justi?ed and their combined costs must not exceed $35,000 in any year of the project period. Capital equipment (i.e., with unit cost over $5,000) is not allowed.
  • The budget should include travel funds for the PD/PI and other senior investigators (up to three people) to attend the annual Network meetings and participate in other network-related activities.
R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

Instead of standard sub-sections, the Research Strategy must consist of the following sub- sections A, B, and C.

Sub-section A. Overall Vision of the Proposed Data Commons and Coordinating Center

In this sub-section, address the following strategic goals:

The scienti?c vision of the proposed PDXNet Data Commons and Coordinating Center;

  • Strategies to establish feasibility and manage risk associated with the activities of the PDCCCes;
  • Major strengths and critical experience of the research team, particularly in coordinating multi-disciplinary and multi-institutional programs (explain collective strengths without repeating information contained in individual biosketches);
  • How the experience of the research team will bring unique capabilities or advantages to a network devoted to the study of the effectiveness of novel therapies against patient-derived models of cancer
  • Innovative and unique aspects of the Center (including institutional environment, infrastructure, personnel) and its potential for coordinating and facilitating the trans-disciplinary research conducted through the entire PDXNet program;
  • The proposed organization and sta?ng of the PDCCC; how key personnel will interact and ensure e?cient cooperation, communication and coordination across the PDCCC, PDTCs, and with NCI and PDMR-FNLCR; and how the proposed organization will create an integrated entity capable of e?ectively providing scienti?c, infrastructure and administrative support for the PDXNet and facilitating the Network’s objectives;
  • The potential benefits the strategic goals and aims of the PDCCC will bring to the overall PDXNet program.

Sub-section B. Leadership and Administration Unit

In this sub-section, address the following aspects:

The structure and organization of the Administrative Unit;

  • Plans outlining the leadership team's collaboration efforts with the PDTCs, FNLCR and NCI program sta? on scienti?c progress, peer- reviewed publications, web sites, evidence-based dissemination, or new collaborations and partnerships;
  • Plans for administrative support for the trans-network collaborative pilot projects, including proposed procedures for solicitation, review, selection, and oversight of such pilot projects;
  • Plans for providing logistical support for the Steering Committee and its sub-committees, working groups (the plan should include co-organizing with the NCI the annual Steering Committee meeting and logistical support for other meetings, teleconferences, etc., as needed); and

  • Plans for other logistical/administrative support that may be needed for the activities of PDXNet.

Sub-section C. PDXNet Data Commons

In this sub-section, address the following strategic goals:

  • Establishing and operating a centralized data collection, management, analysis, and dissemination unit to support the entire PDXNet. This includes the capacity for setting-up a database that collects PDX demographic data, molecular characterization data and drug response data across the network. The data must include information about the regulatory approvals of specimen collections and the level of informed consent for use of the biospecimen;
  • Establishing plans for the analysis of complex data from multiple sources, including molecular characterization of PDX models used in consortium trials and response data collected at the PDTC’s. The plan should include a description of how generated data will be distilled into recommendations for clinical trial designs; and
  • Establishing procedures that would allow for e?cient sharing of PDX models and/or associated data for collaborative research studies as appropriate and consistent with achieving the goals of the program. These procedures should address sharing across the PDXNet as well as with outside investigators, as well as the process for review and approval of requests for access to the specimens and/or data. The procedures should describe the tracking and distribution of available specimens to investigators.
  • Establishing plans to support of electronic information handling, and bioinformatic data storage and data analysis activities across the entire PDXNet.
  • The description must include the following speci?c aspects:
    • Plans to develop a secure internet-accessible interface (include privacy/confidentiality protections) for the PDXNet where each participating PDTC can deposit molecular pro?ling data and PDX preclinical trial data in a standardized format with the required data elements to provide for trans-network collaborative projects;
    • Concepts or strategies to manage data flows and analytics, including but not limited to workflow timelines;
    • Plans to integrate or adapt existing bioinformatics datasets and data platforms (e.g., genomics, proteomics) for application in the participating site e?orts with sharing of tools by individual sites, as appropriate;
    • Plan to work with the PDMR-FNLCR and the PDTCs to ensure there are uniform approaches to molecular pro?ling data standardization to enable data sharing among PDXNet participants;
    • Plans to create new approaches for connections across data types, including various Omics data (e.g., genomics, proteomics);
    • Plans to develop strategies to provide access to all curated data from the participating sites for sharing with the larger research community
    • Plans to coordinate PDTC research within the network including organizational concepts and management strategies
    • Plans for a team approach to establishing and managing a database collection of PDXNet characterization and treatment response data for various PDX models;
    • Approaches to acquiring, curating and packaging PDXNet data

PHS Inclusion Enrollment Report

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

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 also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Do not use the Appendix to circumvent page limits.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) 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 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.

PHS Assignment Request Form

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). 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.

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) 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. See Section III of this FOA for information on registration requirements.

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 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

1. Criteria

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.

Overall Impact

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).

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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 does the proposed Center address the needs of the PDXNet research network that it will coordinate? How is the scope of activities proposed for the Center appropriate to meet those needs? How will successful completion of the aims bring unique advantages or capabilities to the PDXNet research network? How will the Center, as proposed, play an important role in integrating the e?ort of individual PDTCs?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Unit? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing cancer research? Do the investigators demonstrate significant experience with coordinating collaborative research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Unit? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this FOA:

How well does the applicant’s experience demonstrate the ability to oversee selection and management of subawards, if needed? How well have the PD(s)/PI(s) demonstrated experience and an ongoing record of accomplishments in managing multi-institutional cancer research? How well do the investigators demonstrate signi?cant experience with multi-disciplinary and/or multi-institutional programs related to preclinical cancer models and/or anticancer drug testing/development?

Innovation

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research consortium the Unit will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed

Specific to this FOA:

How novel and e?ective are the organizational concepts or management strategies proposed to coordinate the research of PDTCs that the Center will serve? How e?ective and innovative are the concepts or strategies proposed for managing data ?ows and data analytics in coordinating the PDXNet research proposed? How creative are the proposed approaches in terms of the ability to e?ciently engage Network participants, e?ciently implement centralization and standardization of data collection components, etc.? How novel and e?ective are the proposed methods of coordinating, acquiring, curating, and packaging PDXNet data for research use, as well as allowing access to the data for the research proposed?

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?

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?

Specific to this FOA:

How well-reasoned and appropriate are the overall strategy, operational plan, and organizational structure to accomplish the goals of the PDXNet research that the Center will serve? If the resource is in the early stages of operation, how well does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the resource? How appropriate is the plan for work-?ow and the timeline proposed? How adequate are the investigators’ plans to address relevant biological and technical variables inherent in early-passage patient derived xenograft models across multiple sites?

Environment

Will the institutional environment in which the Unit will operate contribute to the probability of success in facilitating the research consortium it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Unit proposed? Will the Unit benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling

Specific to this FOA:

How well does the institutional environment in which the Center will operate contribute to the probability of success in facilitating the PDXNet research network/consortium it serves? How well will the Center bene?t from unique features of the institutional environment, infrastructure, or personnel? How adequate are resources available within the scienti?c environment to support electronic information handling? How su?cient are resources available to support bioinformatic needs for data storage and data analysis activities expected for the PDXNet?

Additional Review Criteria

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

 

 

Leadership and Administration Unit

How adequate are the research infrastructure, programs, and collaborations to support the PDTCs? How adequate are the scientific qualifications and managerial and collaborative capabilities of the proposed Coordinating Center leadership team? How appropriate is the leadership team structure and experience of the proposed Coordinating Center in terms of (a) the overall goals of PDXNet program; (b) the coordination of multiple institutions participating in the PDXNet; and (c) understanding and familiarity with the state of the science in this ?eld of research? Given the administration infrastructure proposed, what is the likelihood that PDCCC will have su?cient capabilities to e?ciently collaborate and interact with the PDTCs, FNLCR and NCI program sta? on scienti?c progress, peer- reviewed publications, web sites, evidence-based dissemination, or new collaborations and partnerships?

PDXNet Data Commons

How appropriate are the proposed plans to create the PDX Data Commons? How adequate is the Coordinating Center team’s capacity and expertise for establishing and managing a database that collects PDX characterization (including clinical annotation and molecular characterization) and treatment response data of all PDX models used in the PDXNet program at all participating sites? How well justi?ed and appropriate are the plans for safeguards for privacy and con?dentiality protections of identi?able data? How adequate is the plan that describes a program that will e?ciently support the sharing of specimens and information across the PDXNet as well as access by extramural collaborating investigators as appropriate and consistent with achieving the goals of the program? How well does the plan enable the tracking and distribution of available specimens to investigators, consistent with achieving the goals of the program? How adequate is the plan to include strategies to integrate or adapt existing bioinformatics tools and data platforms (e.g., genomics, proteomics) for application in the participating site e?orts with sharing of tools with individual sites?

 

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

Additional Review Considerations

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

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.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

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 the NIH Grants Policy Statement.

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Recipient 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.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

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 identify, 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 and 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.

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 75.205and 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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 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 speci?c tasks and activities may be shared among the awardees and the NIH as de?ned below.

An NCI Program Director acting as the Program O?cial 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 PDCCC’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 approved plans;
  • Participate in the development and evaluation of pilot projects, cross-PDXNet Projects, and cross-PDXNet activities that will cross-test novel projects;
  • Serving as a voting member on the PDXNet Steering Committee, including participation in annual meetings, and periodic conference calls, etc.;
  • Cooperate with NCI Project Scientists in the program evaluation process;
  • Accept and implement all scienti?c and practical decisions approved by the PDXNet Steering Committee to the extent consistent with applicable grant regulations;
  • Provide information to the NCI Program Directors concerning progress by submitting annual progress reports in a standard format;
  • Prepare for administrative site visits by NCI sta? members;
  • Take advantage of collaboration with other NCI and NIH initiatives and programs, as appropriate for advancing the PDXNet research program;
  • The PDCCC and the entire PDXNet program will be subject to an internal periodic performance evaluation (conducted by the PDXNet Steering Committee, coordinated by the Chair) and an external evaluation (coordinated by the NCI) at least once per project period of the award. 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 HHS, PHS, and NIH policies;
  • The PDCCC will be expected to share with the PDXNet program knowledge, specimens, data, research materials, and any other resources necessary and relevant to the PDCCC award.
  • Participate in the evaluation of applications from outside investigators for access to resources in PDXNet centers, and collaborate with funded investigators when appropriate;
  • The PDCCC is expected to operate under Standard Operating Procedures (SOPs) developed by the consortium 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; and
  • 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.

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

The designated NCI Program sta? members will have substantial involvement as Project Scientists in the awards under this FOA. The speci?c roles of the substantially involved NCI sta? members include the following activities:

  • Serve as the NCI lead Project Scientists and voting members (collectively having one vote) of the PDXNet Steering Committee;
  • Assist in avoiding unwarranted duplications of e?ort across the PDXNet program;
  • Help coordinate collaborative research e?orts that involve the PDCCC and the multiple PDTCs;
  • Monitor the operations of the PDXNet PDCCC and make recommendations on overall project directions and allocations of funds;
  • Review the progress of PDCCC and speci?c activities shared among the Research Centers (PDTCs) and Coordinating Center.
  • Coordinate an external evaluation of the PDXNet program at least once per project period of the award to document the accomplishments, progress, challenges and outcomes of the Program
  • 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 e?ectively leverage existing NIH/NCI resources and infrastructures;
  • Provide clinical background on agent clinical development to guide the development of PDX trials;
  • Provide a liaison between PDXNet investigators and investigators in the ETCTN to facilitate translation of PDXNet research results into clinical trials;
  • NCI sta? at FNLCR will receive, analyze and characterize PDX models received from PDX Network investigators;
  • NCI sta? at FNLCR will coordinate the development of SOPs to be used by PDX Network investigators;
  • Evaluate the adherence of PDXNet awardees to approved resource sharing plans; and

Areas of Joint Responsibilities include:

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 collectively have one vote;
  • The PD/PI of the PDCCC and a designated senior investigator who will collectively have one vote;
  • The NCI/CTEP Project Science O?cer(s) who will collectively have one vote representing CTEP/NCI; and The PDMR-FNLCR liaison (NCI staff member coordinating PDX model activities) who will have one vote.

The PDXNet Steering Committee will meet at least once per year in a face-to-face meeting. The Chair of the PDXNet Steering Committee will be selected at the ?rst 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 Sta? members and/or Program Sta? members from other Federal agencies.

The PDXNet Steering Committee will have the following primary responsibilities:

  • 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 ideas for pilot projects across the PDXNet as well as criteria for their prioritization and approval;
  • 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 the annual Steering Committee meeting to present scienti?c progress and future plans from PDXNet investigators;
  • Coordinate the PDXNet evaluation of applications from outside investigators for access to resources in PDXNet centers, and coordinate as well as collaborate with funded investigators when appropriate;
  • Establish advisory groups as necessary to ensure the progress of individual Research Centers as well as 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 with conduct an internal 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 signi?cant scienti?c advances.

Dispute Resolution:

Any disagreements that may arise in scienti?c 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 sta? 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 ?rst 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.

3. Reporting

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.

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 $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

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

Scientific/Research Contact(s)

Jeffrey A. Moscow, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6565
Email:  jeffrey.moscow@nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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

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