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
Pancreatic Ductal Adenocarcinoma (PDAC) Stromal Reprogramming Consortium (PSRC) (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
New
Related Notices

  • August 05, 2021 - Pre-Application Webinar for the "PDAC Stromal Reprograming Consortium (PSRC)": RFA-CA-21-041 and RFA-CA-21-042. See Notice NOT-CA-21-106.

Funding Opportunity Announcement (FOA) Number
RFA-CA-21-041
Companion Funding Opportunity
RFA-CA-21-042 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.394, 93.395
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for U01 Research Projects to form the NCI-led PDAC Stromal Reprogramming Consortium (PSRC). The overarching objective of the PSRC is to develop a comprehensive understanding of PDAC tumor progression, its microenvironment (TME) as a tumor fate determinant and the reciprocal tumor-TME interactions that drive clinical outcomes. The information obtained through these comprehensive studies should expose new biology-backed vulnerabilities that will inform the development and preclinical testing of novel interventions in PDAC. Central to the PSRC structural organization is the implementation of multidisciplinary team science approaches that iteratively bridge basic and translational research across the tumor-TME continuum in each U01 Research Project, in trans-PSRC activities, and in collaboration with other NCI-funded mechanisms and programs whenever possible.

Key Dates

Posted Date
July 26, 2021
Open Date (Earliest Submission Date)
October 01, 2021
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, 2021 Not Applicable Not Applicable March 2022 May 2022 July 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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, 2021
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

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications for U01 Research Projects to form the NCI-led PDAC Stromal Reprogramming Consortium (PSCR). The overarching objective of the PSRC is to develop a comprehensive understanding of PDAC tumor progression, its microenvironment (TME) as a tumor fate determinant and the reciprocal tumor-TME interactions that drive clinical outcomes. The information obtained through these comprehensive studies should expose new biology-backed vulnerabilities that will inform the development and preclinical testing of novel interventions in PDAC. Central to the PSRC structural organization are team science approaches that iteratively bridge basic and translational research through the establishment of multidisciplinary teams of basic cancer biologists and translational experts in each U01 Research Project. It is envisioned that each PSRC U01 Research Project will be unified by an overarching scientific theme focused on addressing significant challenges in identification, integration and mechanistic evaluation of tumor and TME elements as co-drivers of PDAC progression and response to therapy. Ultimately, the PSRC FOA intends to support a cadre of U01 Research Projects that collectively represent a range of scientific angles in pursuit of addressing compelling questions and significant barriers in PDAC-TME research, target identification and validation, and clinical intervention.

Background

The overarching goal of this FOA is to develop a community of PDAC researchers that will expand upon traditional tumor-centric studies and ongoing immuno-oncology efforts by emphasizing the identification, integration and mechanistic evaluation of additional TME elements driving PDAC progression and response to therapy. The intent is to adopt a comprehensive “Tumor-TME Co-Organizer” research model in the pursuit of novel biology-backed targets involved in modulating multi-directional tumor-microenvironment dynamics. This expansion is designed to expose new vulnerabilities that will inform the design and testing of more effective combinatorial approaches in pre-clinical platforms and near future clinical evaluation in either NCI-based early phase networks (ETCTN) or by industry and/or cancer centers.

Etiology of PDAC

PDAC is currently the fifth most common cause of cancer mortality in the US, but its incidence is on the rise and some estimates project it will become second on the list by 2030. Upwards of 80% of patients present with locally-advanced disease and are not eligible for curative surgical approaches. Standard of care for advanced PDAC remains highly ineffective and involves combinations of surgery, chemotherapy and radiation that target the tumor mass. For decades, systemic palliative gemcitabine treatment was the best option, followed by the introduction of the FOLFIRINOX (combined 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) regimen – which only extended the median overall survival from 6.8 to 11.1 months. Recent attempts to strategically (but narrowly) focus on enhancing drug delivery and modulating the immune microenvironment (TiME) celebrated first partial successes, but have not yet lived up to its promise in changing the bleak 5% 5-year survival rate, including for patients who present with localized disease.

PDAC is characterized by a desmoplastic reaction that results in dense stroma, consisting of abundant extracellular matrix (ECM) and stromal cells, including cancer-associated fibroblasts (CAFs), immune cells, adipocytes, endothelial cells and neurons. Collectively, PDAC stroma constitutes 80% to 90% of the tumor volume and contributes substantially in promoting all aspects of PDAC development and progression - including therapy resistance and metastasis as key characteristics of its recalcitrant nature. Both chemo and targeted therapies designed to disrupt tumor cells have not been very effective in treating or improving PDAC patient survival; and neither have alternative strategies substantively aimed at disrupting the TME compartment of the tumor. While basic and translational researchers alike recognize the importance of targeting microenvironmental elements as part of a strategic blueprint, the approach taken thus far lacks strong mechanistic insight and/or adequate consideration of the TME heterogeneity and its active/instructive role in dictating the fate of tumor cells within a tumor-TME co-organizer structure. CAFs, for instance, are known to be a primary source of collagens, fibronectin and hyaluronic acid that ultimately create a dense, stiff and impenetrable physical barrier with increased interstitial fluid pressure capable of collapsing tumor vasculature, creating an immunologically cold environment, and inevitably blunting drug delivery and response to wide-ranging immune therapies, including immune checkpoint inhibitors . Attempts to disrupt the ECM and interstitial fluid pressure with pegylated hyaluronidase (PEGPH20) or elimination of tissue-resident CAFs with Halofuginone – a pancreatic stellate cell inhibitor – show only modest results; while targeted disruption of Sonic Hedgehog (Shh), Discoidin Domain Receptors 1 & 2 (DDR1 & 2) or TGFß had devastating effects. Shh disruption achieves the objective of eliminating aSMA+ CAFs, but lack of Shh signaling also induces more aggressive and undifferentiated tumors in mice and worse outcome in patients treated with chemo-Shh combinations relative to chemo alone. Small molecule DDR1/2 inhibitors and TGFß-SMAD blockers may reduce overall production of fibrillar collagen and aSMA+ CAF numbers, but they do not address the real threat that other subtypes of CAFs (including iCAFs and apCAFs) have on modulating tumorigenesis through their contributions to inflammation and putative immune-modulatory capacity, respectively. Furthermore, canonical TGFß signaling is tumor-suppressive in a context-dependent manner – often overlooked but may explain why PDAC genetically engineered mouse models (GEMMs) treated with pharmacologic inhibitors of TGFß have a worse prognosis.

Current Treatment Strategies for PDAC

Thus far, clinical studies testing for PEGPH20 with chemotherapy ± immune checkpoint inhibitors are ongoing, along with DDR1-based pre-clinical models to evaluate its effects on the immune landscape, but none of the studies or clinical activities are being informed by parallel basic tumor microenvironmental studies on CAF subtypes ; their multiplicity of origins – including mesenchymal stem cells and trans-differentiation of myocytes, adipocytes, epithelial and endothelial cells; their highly plastic cell states/phenotype switching; or studies on other stromal elements such as endothelial cells, neurons and infiltrating adipocytes. PDACs are known to be well innervated, yet the role of intimate neural–tumor interactions in tumorigenesis and progression is poorly understood; as is the case with endothelial-tumor interactions or cancer-associated adipocytes and CAFs in actively instructing tumor aggressiveness – and recently established in other solid tumor platforms such as melanoma, breast, lung and colorectal cancers.

More recent breakthroughs in treatment strategies and target identification appear to focus on important – yet tumor- and/or immune-centric events involving the use of oncolytic viruses to reprogram the TiME or small molecule-based disruption of cell cycle regulators, DNA repair machinery, mitochondrial/organelle function and tumor cell plasticity. Within this context, most of the basic and preclinical testing platforms developed to date – ranging from cell lines, genetically engineered mouse models and xenografts, and organoid cultures – do not encompass the complete PDAC microenvironment; and may require further development before being useful for comprehensive studies on PDAC tumor-TME dynamics and response to therapy. The same holds true for imaging technologies, where a better characterization of the microenvironmental landscape at the cellular and molecular levels will be instrumental in guiding the adoption of new pathological parameters designed to longitudinally measure the contribution of TME in driving disease state, progression and response to therapy.

The PSRC is designed to build upon and replace the Pancreatic Cancer Microenvironment Network (PaCMEN) and complement other ongoing NCI-sponsored programs such as the Pancreatic/GI SPOREs, RAS Initiative, Pancreatic Cancer Cohort Consortium, and Pancreatic Cancer Detection Consortium. Collectively, these NCI programs are exploring various facets of PDAC etiology, prevention, detection, risk stratification, and treatment – but not within the tumor-TME co-organizer focus presented herein. The long-term goals of the PSRC are to:

  • Allow the most advanced scientific and clinical teams of PDAC investigators to develop an integrated community to collectively and synergistically challenge the tumor as organizer dogma;
  • Identify, characterize and introduce new targetable TME leads based on comprehensive basic/mechanistically dissected tumor-microenvironment dynamics;
  • Develop and/or optimize basic and preclinical research platforms suitable for co-organizer evaluation; and
  • Afford PSRC members and affiliates the option to utilize data generated from their PSRC project(s) to inform and/or conduct separately funded early clinical trials, particularly with agents developed at the grantee institution or in collaboration with industry.

Research Objectives and Main Requirements for this FOA

All proposed PSRC U01 Research projects must include the following main attributes (for additional details of the requirements, please see Section IV Application and Submission Information).

  1. Overall Research Focus: Each proposed U01 Research Project must articulate an overarching scientific theme and hypothesis(ses) that focus within the broad areas of tumor and TME as co-drivers and co-enablers (i.e., tumor-TME co-organizer model) of disease progression and resistance/response to therapy.
  1. Research Project Teams and Organizational Structure: Each proposed U01 Research Project should consist of:
  • A multi-PI structure that integrates research (and associated expertise) across the basic/mechanistic biology and preclinical/translational spectrum; and
  • Integration of a minimum of one (1) basic/mechanistic science and one (1) preclinical/translational science research area – as exemplified below in (C) – in order to establish an iterative Research Project that aims to generate biology-backed leads that may inform early phase clinical trials.
  1. Areas of Scientific Priority and Interests: Advancements that may comprehensively inform future PDAC clinical management will require strong integration between basic/mechanistic and preclinical/translational areas of research, along with built-in capabilities to facilitate and support both arms.

Examples of basic/mechanistic science may involve but are not limited to studies on

  • Non-immune cellular microenvironment-driven tumor phenotype
    • Functional role of stromal cells (endothelial cells, neurons, adipocytes) and the microbiome in driving/instructing epithelial cell phenotype and adoption of invasive/metastatic potential.
    • Mechanistic elucidation of inherent or acquired CAF cell state/subtype(s) involvement in tumor evolution or response to therapy.
    • Defining the (multi)-functional role of key tumor-cell centric mutations/driver genes/epigenetic modulation in TME elements.
    • Evaluation and biological characterization of TME response to standard of care or experimental therapeutics originally designed to target tumor mass.
  • Extracellular matrix (ECM)-mediated structural and/or mechanosignaling effects
    • Functional role of tumor-associated and/or normal ECM in reprogramming epithelial cell behavior, plasticity or resistance to therapy.
    • Evaluation of ECM density and heterogeneity in eliciting tumor cell response to tissue stiffness, chemokine/cytokine distribution and nutrient availability/bioenergetic changes.
    • Effects of targeted ECM remodeling in stromal cell-tumor cell dynamics.

Examples of preclinical/translational science may involve but are not limited to:

  • In depth characterization of the human PDAC TME over the course of the disease, pre- and post- interventions combined with mechanistic studies beyond correlations or cataloging of cell types in the microenvironment.
  • Novel interventions targeting components of the PDAC TME including stroma, immune response, epithelial-mesenchymal transition, tumor vascularization, etc.
  • Models mimicking the interactions between PDAC and its microenvironment.
  • Data generated from Lynch syndrome- and/or microsatellite instability-associated PDAC responses to combination therapies and their utilization for the design of interventions in PDAC not-associated with these conditions.
  • Development of prediction assays for PDAC patient stratification in combination therapy interventions.
  • Preclinical testing of targeted therapies or in combination with radiation, or chemotherapy.
  • Research in age, sex, and racial/ethnic disparities-associated PDAC microenvironment and the potential to use of targeted therapies in these populations.
  • Exploration of the role of TME components in the metastatic spread of PDAC
  • Study of TME in distal/metastatic sites

Examples of built-in capabilities to develop and optimize models, approaches and technologies to feed into both the basic and translational studies – including capabilities that would enable comprehensive basic/mechanistic-pre-clinical/translational studies in underrepresented areas of age, sex, and racial/ethnic disparities – may pertain but are not limited to

  • Access to catalogued specimens from collaborative early phase clinical trial(s).
  • Collection/library of organoid cultures or patient-derived xenografts from PDACs, which maintain the original architecture of the tumor, to allow sufficient expansion for a detailed molecular/multi-omic analysis.
  • Novel or repurposed PDAC platforms – including repurposed in vivo genetic models - to interrogate complex ECM-stromal cell-tumor cell interactions (with non-immune cells at its core) in tumor progression and resistance to therapy – along with companion human tissues (biopsies from clinical trials, rapid autopsies, or patient-derived models).
  • Computational and systems biology infrastructure to develop in silico tumor evolution models.

Non-Responsive Applications

The following Research Projects would be considered non-responsive to the PSRC RFA:

  • Applications that do not propose a combination of basic/mechanistic areas and preclinical/translational areas of study;
  • Applications that are not hypothesis testing;
  • Applications that do not propose to study PDAC across the tumor-TME continuum; or
  • Applications that focus solely on tumor cell intrinsic and/or immune-oncology studies that fail to triangulate with non-immune stromal elements.

Effort Coordination

Each PSRC U01 Research Project must have appropriate logistical support for the expected administrative, communication, and coordination needs. Said support will be instrumental in integrating and synergizing the activities within the U01 Research Project and across the PSRC Program as a whole.

Coordination with PSRC Coordinating and Data management Center (CDMC): The PSRC Program will have a CDMC using the U24 Resource-Related Research Project Cooperative Agreement mechanism that will support the overall network coordination including facilitating steering committee and working group meetings, integrating efforts across the network, facilitating research collaborations, soliciting and coordinating pilot projects, data and unique resource management, and network evaluation.

PSRC Working Groups, PSRC-CDMC Coordination and Intra-PSRC and/or External Collaborative Projects: The PSRC program will support an integrated and interdisciplinary approach to identify and comprehensively characterize the complex crosstalk between tumor-intrinsic and extrinsic/ microenvironmental drivers in dynamically co-regulating progression and resistance/response to therapy. Individual U01 sites are not expected to exhaustively tackle the myriad of angles as exemplified above, but collectively the program may uncover strong – yet previously unknown – candidate pathways and determinants of progression and resistance worthy of testing across PSRC U01 sites; along with the identification of common technical, logistical and experimental challenges. For these reasons, NCI expects a steering committee and cross-cutting set of working groups to be established by the network; and for resources, tools and expertise to be freely exchanged between the program participants and the scientific community at large. This exchange will also be facilitated by the CDMC and through required formal bi-annual steering committee meetings and monthly video-conference calls.

The PSRC program will also include intra-network collaborative pilot studies and/or collaborative efforts with non-PSRC/external investigators that are supported with pre-established 15% restricted funds from each award for years 2-5 of the Program. PIs for the U01s are expected to identify common areas of interest and cross-cutting research platforms with other NCI-funded sites within or outside the network, and to develop a research proposal and leadership plan that outlines the scientific strategy and roles and responsibilities of each contributing investigator.

Governance of the NCI PSRC Program

The PSRC program (encompassing the U01 Research Projects and U24 CDMC) will be governed by a PSRC Steering Committee (SC). The SC will oversee and coordinate the activities of all trans-PSRC activities. Details on the composition and functions of the SC are provided in Section VI. Award Administration Information, Terms and Conditions of Cooperative Agreement, “Areas of Joint Responsibility.”

Evaluation of the Program

PSRC awardees will be expected to participate in an external evaluation process that will be coordinated by NCI Scientific Staff. This evaluation will largely be based on the overall progress towards achieving the scientific goals of the entire PSRC Program. The evaluation will access the quality and innovation of the research conducted by the PSRC, progress of the Research Projects, and effectiveness of the collaborative projects. Specific aspects may include: peer-reviewed publications, achievements of planned milestones, development of infrastructure and research capacity, efficiency of resource and data utilization and sharing arrangements as appropriate among PSRC sites (as described in Section VI).

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

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.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NCI intends to commit $5.94M in FY 2022 to fund up to 6 awards.

Future year amounts are anticipated to be at the same levels but will ultimately depend on annual appropriations.

Award Budget

Application budgets for each U01 may not exceed $600K in direct costs per year and need to reflect the actual needs of the proposed project.

Award Project Period

Applicants may request up to 5 years of support.

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 Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

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.

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

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

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

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.  This means that the NIH will not accept:

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

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:

Peter Ujhazy, MD, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5686
Email: pu5s@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 Other Resources: In addition to standard items, applicants must describe the following:

  • The specialized or unique facilities, core resources, and services that each U01 team will leverage towards achieving the objectives of the proposed studies. List platforms, technologies, tools, access to instruments and specimens/tissues, in vivo, in vitro and/or in silico model systems necessary to accomplish proposed aims and how said technologies and materials uniquely position the team to achieve the overarching goals of the PSRC Program.
  • The expert technical or advisory personnel and information of other components of the supporting infrastructure pertinent to the application.
  • Any relevant ongoing institutional, and/or private sector support and resources that augment or complement resources for which funding from this FOA is sought; and how said resources may be available and accessible to the PSRC Program.
  • Available laboratory information management system, analysis tools, data storage, security, archiving, and retrieval systems. Applicants must also describe standardized formats for data reporting and the validation process for data prior to submission to the U24 and/or NCI Cancer Research Data Commons for data evaluation and data mining across the PSRC Program, and public access.
SF424(R&R) Senior/Key Person Profile

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

In addition, the following specific requirements must be addressed:

  • Each team must have expertise in basic/mechanistic and preclinical/translational research. A PSRC U01 application must designate at least two PDs/PIs (a clinician familiar with unmet clinical needs, clinical trials, with access to trial samples; and a proteomics researcher).
  • Each team should also have expertise in tumor and TME biology of PDAC.
  • Given the need for integration of multidisciplinary efforts in each PSRC U01, the scientific leadership and other senior members of the team are expected to have considerable experience in collaborative, multidisciplinary hypothesis-driven research and development across the basic-translational spectrum.

R&R or Modular Budget

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

Additional guidance applies, as specified below:

Leadership Effort Commitment: The PSRC multi-PD/PI must each commit and maintain through the life of the award a minimum of 1.2 calendar months of effort.

Restricted funds: The budget should include funds (15% of the overall PSRC Research project budget) for trans- or extra-PSRC collaborative pilot projects for years 2-5. The process for solicitation and prioritization of collaborative project proposals will be developed within each PSRC Research Project. The PSRC Steering Committee will prioritize pilot project proposals and submit recommendations to the NCI for further consideration and approval. The collaborative project funds should be listed in the Other Expenses category under the heading "Restricted Funds".

Travel Funds: The budget should include travel funds for the PD(s)/PI(s) and at least 2 junior members of the U01 team to attend the annual or biannual PSRC Steering Committee meetings and participate in other network-related activities.

Other: It is expected that funds will be allocated to open-access publishing.

Site visits. Because of the complexity of the PSRC, NIH/NCI Program Staff members may conduct annual administrative site visits. PSRC applicants should be prepared for annual visits and should budget appropriately (including travel for collaborators and other necessary costs).

Note: Capital equipment requests (for equipment over $5,000) are not allowed under this FOA.

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:

Specific Aims: Describe the specific aims for the PSRC U01 Research Project to address questions of PDAC biology across the tumor-TME continuum as co-organizers in progression and/or resistance to therapy, including major milestones. In addition to a brief description of the hypothesis-testing specific aims and approach(es) to be employed, applicants must outline the scope of the proposed research and its relevance to a specific unmet biology-backed clinical need in order to improve the outcome of a treatment.

NOTE: The Specific Aims should represent a balance and integration of basic/mechanistic and preclinical/translational areas and include the proposed use of biologically and clinically meaningful research platforms and resources.

Research Strategy: It is anticipated that the breadth of a PSRC U01 Research Project will be comprehensive and encompass basic/mechanistic biology and preclinical/translational perspectives to test an overarching hypothesis that spans across the tumor-TME continuum. Describe the vision of the PSRC U01 Research Project that will guide integration and iteration between Aims and Built-In Capabilities.

Instead of the standard sub-sections defined in the Application Guide, Research Strategy must consist of sub-sections as defined below.

Sub-Section A. PSRC U01 Research Project Framework. Describe the framework with respect to the project design of a minimum of one (1) basic/mechanistic research area and one (1) preclinical/translational research area. Justify the rationale for the chosen framework;

Sub-Section B. PSRC U01 Research Project Integration and Iteration. Describe how the PSRC U01 Research Project will foster integration and iteration between the basic/mechanistic and preclinical/translational aspects in line with testing the central hypothesis that defines the Project. Describe how the PSRC Research project will demonstrate leadership in the context of driving a productive collaborative atmosphere of integration and iteration that bridges basic/mechanistic and preclinical/translational research across the tumor-TME continuum.

Sub-Section C. Research Innovation. Describe how the PSRC Research Project innovates in comprehensively deciphering the mechanistic underpinnings and clinical challenges of PDAC biology and resistance to therapy;

Sub-Section D. Research Teams. Summarize the major collective strengths of the multidisciplinary team(s) in the proposed areas of research. Explain how the chosen expertise set represented by the respective team members (e.g., cancer biology, molecular medicine, translational science, computational biology, bioinformatics, others) will be integrated to advance the proposed Research Project; describe the environments (e.g., academic or other entity) of the research team members and how they will support the mission of the proposed PSRC U01;

Sub-Section E. Built-In Capabilities. Briefly explain the unique resources that will be leveraged in the U01 Research Project and indicate how said resources will be utilized in both basic/mechanistic and preclinical/translational arms of the Project.

Letters of Support: Include a letter of support from an institutional official endorsing the proposed PSRC U01 Research project and describing available institutional resources to support the research. Also include letters from investigators who will serve as consultants or collaborators on the project but with no measurable efforts. Do not include letters from investigators who will have committed efforts in the application. In addition, Letter(s) must also specify the following parameters:

  • Intellectual Property: Consistent with achieving the goals of the PSRC and maximizing the benefit of all research funded as part of the Program for the improvement of public health through discoveries of the scientific community, PSRC Data Sharing and Data Release policies expect a broad freedom-to-operate for all users of PSRC data (e.g., by rapidly placing all data in the public domain). In addition, computer algorithms produced specifically to analyze PSRC data, software source code or other resources (reagents) made possible under the auspices of PSRC are expected to be made broadly available. It is expected that any data producer in the PSRC Projects will make all information available, without requirement for licensing, for applications such as, but not necessarily limited to, the use of markers in developing assays or targets for therapeutic and diagnostic purposes. All PSRC members and affiliated institutions must acknowledge agreement to this PSRC Intellectual Property Policy. Investigators and their institutions must expressly acknowledge and agree to abide by this policy.

Note that the NCI Program Staff may negotiate modifications to these plans prior to funding.

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, must include and address a Resource Sharing Plan as defined below.
  • A Resource Sharing Plan for data (including genomic data), unique materials (including biological materials such as patient-derived cells, organoids and tissues), tools, model organisms, reagents and therapeutics, along with IP and knowhow management must be provided by each PSRC U01 Research Project application and must cover all the activities proposed for the PSRC U01 Research Project and within the context of the PSRC Program, where applicable.
  • Resource Sharing Plan should briefly describe the types of data and computational resources and unique biological resources that are expected to be generated and shared, consistent with achieving the goals of the PSRC Program;
  • Resource Sharing Plans are expected to describe plans for anonymization, annotation, multimodal data integration; harmonization; transfer learning; development of robust statistical-, Artificial Intelligence-, and/or Machine Learning-ready datasets to facilitate formats that are accessible to increase the value of these data and unique resources for sharing with the scientific community and the PSRC CDMC;
  • Formats, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this FOA are expected to be compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Bioinformatics platforms (https://cbiit.cancer.gov/data-sharing).

Note that NCI Program staff may negotiate modifications to these plans prior to funding. Specifically, applicants will be expected to abide by the policies and procedures for unique resources and data, software, and computational model sharing within the context of the NCI Cancer Data Ecosystem including infrastructure and resources for access of multi-modal data, elastic computation, and analysis through the Cancer Research Data Commons developed upon availability (see Section VI: Terms and Conditions of Cooperative Agreement).

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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.

Foreign Institutions

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

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review 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.

For this particular announcement, note the following:

The Research Project will be assessed for its integration and synergy across the aims for bridging required basic/mechanistic and preclinical/translational aspects of the studies in addressing the complexities of tumor-TME as a co-organizer of PDAC progression and resistance to therapy.

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: What is the potential for wider adoption of the technical or conceptual innovation developed by the PSRC Research Project to inform comprehensive understanding of how the tumor-microenvironment continuum contributes to PDAC progression and resistance to therapy in the long-term? Do the results generated by the PSRC Research Project have potential for wider adoption to inform basic research, clinical trial design, and/or patient outcomes?

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 the PSRC Research Project combine/integrate expertise across basic, pre-clinical, and clinical areas of investigation? How qualified are the applicant PD(s)/PI(s) to lead research in their respective fields and with experience in managing multidisciplinary and integrative team science?

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 PSRC Research Project uniquely innovate in ways to integrate-iterate across the basic/mechanistic and preclinical/translational cancer research spectrum?

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 does the design of the proposed PSRC Research Project involve hypothesis-driven approaches that bridge basic/mechanistic and preclinical/translational approaches to address PDAC progression and resistance to therapy in the tumor-microenvironment continuum? How well matched are the Built-In Capabilities to the needs of the overall Research Project? Are the services of the Built-In Capabilities essential to the goals of bridging the basic/mechanistic and preclinical/translational aspects of the Research Project?

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 does the scientific environment at the participating sites stimulate trans-disciplinary research collaborations? How well does the environment facilitate multidisciplinary relationships and the iterative flow between basic/mechanistic and preclinical/translational researchers? How conducive are the Resource Sharing Policies for the sharing of data, model organisms, human and non-human specimens, tools, reagents, therapeutics, genomic data, intellectual property, know-how and proprietary techniques and inventions within and outside the institution, especially with other members of the PSRC? How much freedom to operate is granted to PSRC members to utilize, without restrictions other than by law(s) or regulation(s) said Resources for non-commercial purposes directly related to the PSRC activities and goals?

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.

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

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 Resource Sharing Plans are reasonable and aligned with the PSRC objectives.

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 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.

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.

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

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

Institutional Review Board or Independent Ethics Committee Approval: 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 awardee 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. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 , 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

  • Participate in the annual or biannual PSRC Steering Committee meeting, periodic conference calls organized by the PSRC CDMC, and collaborative PSRC activities.
  • Participate in the development of various topical scientific working groups;
  • Identify and promote opportunities for PSRC research and coordination, including collaborative pilot projects and validation of experimental concepts and observations.
  • Identify and promote trans-PSRC and external collaborations to advance PDAC basic/mechanistic-preclinical/translational research.
  • Abide by the governance of the PSRC and all program policies agreed upon by the PSRC Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations.
  • Report progress to the NCI Program Officials on all PSRC research and activities annually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by program staff members on a semi-annual basis.
  • In conjunction with the PSRC CDMC, ensure that data are deposited in a timely manner in appropriate publicly available databases, and that models, software, and other tools and resources developed as part of this Research Project are made publicly available according to PSRC policies.
  • Ensure that results of the Research Projects are published in a timely manner.

The following additional responsibilities will also apply for each PSRC U01 Research Project awardee:

  • 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.
  • Participating PSRC members are also encouraged to organize and participate in other PSRC Program meetings and workshops, organize collaborative activities, and promote Trans-PSRC collaborations, and organize and participate in scientific and programmatic working groups.

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

  • Serve as NCI lead Project Scientists and voting members of the PSRC Steering Committee;
  • Serve as resource for PSRC in promoting interactions with other ongoing NCI activities that may be relevant to the goals of PSRC;
  • Assist in avoiding unwarranted duplications of effort across the PSRC Program;
  • Facilitate collaborative research efforts that involve multiple PSRC Research Projects.
  • Evaluate the effectiveness and facilitate Program-wide adoption of resource practices;
  • Monitor operations and conduct programmatic evaluations through site visits;
  • Make recommendations on overall project directions;
  • Make funding decisions on collaborative pilot projects supported through the PSRC Research Project restricted funds;
  • Reviewing the progress of activities shared among the PSRC U01 Research Projects and U24 CDMC;
  • Participate in organizing PSRC meetings, specialized workshops, and webinars;
  • Additionally, an agency program official or IC program director will be responsible for the standard scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

PSRC Program will have a Steering Committee as a governing body. The PSRC Steering Committee will consist of the following voting members:

  • The PDs/PI(s) of each awarded PSRC Research Project (or senior investigator as proxy when applicable) will collectively have one vote;
  • The PD/PI of the CDMC will collectively have one vote; and
  • The NCI Project Scientists that collectively have one vote for the NCI.

Additional NIH/NCI program staff and other government staff may participate in PSRC Steering Committee meetings as non-voting members. The structure is designed to allow awarded investigators and NCI staff to work together to facilitate trans-PSRC activities based on synergistic expertise and projects.

Two PD(s)/PI(s), representing two different PSRC U01 Research Projects, will be selected to serve as co-chairs of the Steering Committee on a rotating basis following award issuance. All PSRC Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The Steering Committee may have additional non-voting members.

The PSRC Steering Committee will meet annually or biannually at the PSRC Annual Steering Committee Meeting and as needed through monthly virtual meetings. The PSRC Steering Committee will:

  • Identify scientific and policy issues that need to be, or can benefit by being, addressed at the PSRC Program level and develop recommendations to NIH/NCI Program Officials for addressing such issues;
  • Establish, as necessary, subcommittees to ensure progress of the individual PSRC Research Projects the PSRC Program;
  • Review the potential of shared support infrastructure(s) at individual Research Projects to serve the needs of other PSRC Research Projects and the entire PSRC Program;
  • Develop procedures for soliciting and evaluating ideas for pilot project across the PSRC as well as criteria for their prioritization and approval;
  • Ensure that the Research Projects and CDMC take advantage of existing NCI and NIH resources and programs;
  • Participate in the development of the agenda for the annual or biannual Steering Committee meeting to present scientific progress and future plans from PSRC investigators; and
  • Coordinate dissemination of PSRC Program output to the broader cancer research community.

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.

3. Reporting

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

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

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

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

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)

For Preclinical and Translational aspects, contact:

Peter Ujhazy, MD, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5686
Email: pu5s@nih.gov

For Basic and Mechanistic aspects, contact:

Jeffrey Hildesheim, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6213
Email: hildesheimj@mail.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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