Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Cancer Institute (NCI)
U01 Research Project Cooperative Agreements
Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) is soliciting applications for the Research Units (RUs), one of the two scientific components of the Pancreatic Cancer Detection Consortium (PCDC), to conduct research on early detection of pancreatic ductal adenocarcinoma (PDAC) and characterization of its precursor lesions to identify those patients who are at high risk of progression to cancer. The PCDC will continue to address one of the four research priorities identified in the NCI's 2014 Scientific Framework for Pancreatic Ductal Adenocarcinoma (PDAC). The PCDC will support research for the development and testing of new molecular and imaging biomarkers for detecting PDAC early and for identifying those patients at high risk of PDAC (because of genetic factors or presence of precursor lesions) who could be candidates for early intervention. The PCDC-RUs will consist of multi-disciplinary teams and will undertake studies to: identify and test biomarkers measurable in bodily fluids for early detection of PDAC and/or its precursor lesions; develop molecular- and/or imaging-based markers of pancreatic cysts and determine which ones are likely to progress to cancer; develop molecular- and/or imaging-based approaches for screening populations at high risk of PDAC; use machine learning and computational approaches towards biomarker discovery and/or validation; and conduct biomarker validation studies. The PCDC-RUs will also collect longitudinal biospecimens for building a biorepository. Each PCDC-RU is expected to participate in collaborative activities with other PCDC-RUs and share ideas, biospecimens, and data within the Consortium.
The other scientific component of the PCDC will be the Management and Data Coordination Unit (MDCU; see companion PAR-21-335). The PCDC-MDCU will provide support toward study design, protocol development, statistical analysis, coordination, harmonization, data management and stewardship for the trans-PCDC collaborative projects, including biorepository building effort. The PCDC-MDCU will also support the coordination and organization of Consortium-wide calls, meetings and workshops.
30 days prior to 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 15, 2021 | November 15, 2021 | Not Applicable | March 2022 | May 2022 | July 2022 |
| June 10, 2022 | June 10, 2022 | Not Applicable | November 2022 | January 2023 | April 2023 |
| October 11, 2022 | October 11, 2022 | Not Applicable | March 2023 | May 2023 | July 2023 |
| February 10, 2023 | February 10, 2023 | Not Applicable | July 2023 | October 2023 | December 2023 |
| June 13, 2023 | June 13, 2023 | Not Applicable | November 2023 | January 2024 | April 2024 |
| October 11, 2023 | October 11, 2023 | Not Applicable | March 2024 | May 2024 | July 2024 |
| June 11, 2024 | June 11, 2024 | Not Applicable | November 2024 | January 2025 | April 2025 |
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.
Not Applicable
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.
Purpose
Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) is soliciting applications for the Research Units (RUs), one of the two scientific components of the Pancreatic Cancer Detection Consortium (PCDC), to conduct research on early detection of pancreatic ductal adenocarcinoma (PDAC) and characterization of its precursor lesions to identify those patients who are at high risk of progression to cancer. The other scientific component of the PCDC will be the Management and Data Coordination Unit (MDCU). The PCDC will support research for the development and testing of new molecular and imaging biomarkers for early detection of PDAC and/or for identifying those patients at high risk of PDAC (because of genetic factors and/or family history or presence of precursor lesions) who could be candidates for early intervention.
Clinically useful screening markers should be present in those patients with high-grade precursor lesions (intraductal papillary mucinous neoplasm [IPMN], mucinous cystic neoplasm [MCN], and pancreatic intraepithelial neoplasia-grade 3 [PanIN-3]) and early-stage PDAC, while absent in those without neoplasia, such as pancreatitis. These biomarkers should be readily detectable in easily obtainable biofluids, ideally collected using non-invasive or minimally-invasive techniques (e.g., blood, saliva, urine, stool, cyst fluid, pancreatic juice).
Key Definitions for this FOA
PCDC-Research Units (RUs; this FOA): The PCDC-RUs will consist of multi-disciplinary teams and will undertake studies to: develop and test biomarkers measurable in bodily fluids and imaging methods for improved detection of early-stage PDAC, and high-grade lethal precursors (IPMNs, MCNs, PanIN-3s); develop and test biomarkers and imaging methods to determine which mucinous neoplasms (IPMNs and MCNs) are likely to progress to cancer; study cancerization of pancreatic ducts to identify biomarkers that can help detect cancer early; develop molecular- and/or imaging-based approaches for screening populations at high risk of PDAC to detect cancer early; use machine learning and computational approaches for biomarker discovery and/or validation; conduct biomarker validation studies; and collect prospective, longitudinal biospecimens for contribution to a biorepository. Each PCDC-RU is expected to participate in collaborative activities with other PCDC-RUs and share ideas, biospecimens, and data within the Consortium.
Preferred Expertise: The multidisciplinary teams should include biologist(s), epidemiologist(s), pathologist(s), radiologist(s), statistician(s), clinician(s), a research coordinator, and investigators with imaging expertise (if applicable). Each PCDC-RU will be supported by an individual U01 cooperative agreement award.
PCDC-Management and Data Coordination Unit (MDCU; companion PAR-21-335): The PCDC-MDCU will provide support toward study design, protocol development, statistical analysis, coordination and data management of trans-PCDC collaborative projects, biorepository building, and organizational and logistics support for Consortium-wide calls, meetings and workshops. The PCDC-MDCU will be supported by the companion U24 cooperative agreement award.
Biomarker Definition. In the context of this FOA, biomarkers are defined as cellular, morphological, biochemical, molecular, histological, and imaging (molecular or radiographic) characteristics by which normal and/or abnormal biological processes can be recognized and/or monitored. Biomarkers are measurable in biological materials, such as, in tissues, cells, and/or bodily fluids.
Background
Pancreatic Cancer: Pancreatic cancer is the third leading cause of cancer-related mortality in the United States and is projected to move up to the second position by 2030. The poor prognosis of pancreatic cancer is primarily due to the diagnosis of the disease at advanced stages as patients often present with locally advanced or metastatic disease where resection is not feasible. The lack of symptoms or presence of non-specific symptoms at early stages makes it challenging to detect this cancer early. The earlier the pancreatic cancer is detected, the better the chance a person has of surviving longer. Surgical resection is currently the only potentially curative treatment, but only 15-20% of patients are candidates for surgery, and recurrence rate is still high among resected cases. The Recalcitrant Cancer Research Act of 2012 called upon the NCI to identify and make progress on recalcitrant and deadly malignancies with a 5-year relative survival rate of less than 20% and estimated to cause at least 30,000 deaths per year. Pancreatic cancer is a recalcitrant cancer with a 5-year relative survival rate of 10.8%, and an estimated 60,430 new cases, and 48,220 deaths in 2021, according to the Surveillance, Epidemiology, and End Results (SEER) Program’s Cancer Statistics Facts (Pancreatic Cancer Cancer Stat Facts). The most prevalent type of pancreatic cancer is PDAC, representing >90% of all pancreatic malignancies. The NCI 2014 Scientific Framework for Pancreatic Ductal Adenocarcinoma identified four research priorities based on the recommendations of an expert panel of extramural scientists convened by the NCI. One of the specific initiatives recommended by this panel was Evaluation of longitudinal screening protocols concomitant with the development of new molecular and imaging biomarkers for patients at high risk for PDAC (because of genetic factors or the presence of mucinous pancreatic cysts) who could be candidates for early surgical intervention. The NCI PCDC was established in 2016 to address this recommendation.
The majority of PDAC is sporadic, i.e., occurring without a family history or a genetic predisposition of the disease. It is estimated that it takes more than 10 years before an initiating mutation in a normal pancreas cell progresses to the non-metastatic parental founder cell of PDAC, and at least five more years are required for the acquisition of metastatic ability. This window of time offers an opportunity for curative interventions if the disease could be diagnosed at an earlier stage. It is noteworthy that recent evidence also supports the hypothesis that once PDAC becomes detectable, the clinical progression from early-stage to advanced-stage disease is rapid; therefore, the best outcomes will be tied with detection at the earliest stages of the disease. Despite substantial advancement in technologies and progress towards identifying biomarkers for early detection of the disease, there remains a need for the development of better molecular, imaging and/or integrated molecular and imaging approaches that are highly discriminating for pancreatic cancer and clinically useful. For patients with a strong clinical and radiological suspicion of PDAC, having a highly discriminating, non-invasive tool may expedite patients diagnostic workups so that they could proceed to receive treatment. Alternatively, for patients with a low suspicion of PDAC based on clinical information and radiologic imaging, having a highly discriminating, non-invasive tool should obviate additional costly workups. Another area of impact involves those patients with a high risk for developing PDAC, who do not need immediate clinical intervention but can be surveilled instead.
Current PCDC Overview: Currently available modalities for screening those at high risk of pancreatic cancer are mostly anatomical imaging methods, including traditional cross-sectional imaging such as abdominal ultrasound or computed tomography (CT), or imaging used in surveillance protocols such as magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS), or CT when MRI and EUS are not possible. Traditional cross-sectional imaging has little role in screening for sporadic pancreatic cancer. The question then arises, whom to screen? Given the low prevalence of PDAC, it is advantageous to first focus on developing better tests for screening those at high risk of the disease, as outlined in the Scientific Framework recommendation mentioned earlier. The PCDC currently focuses on two main types of high-risk populations that are outlined below:
(1) Individuals at high risk of developing PDAC because of genetic factors, i.e., presence of germline variants in cancer susceptibility genes that includes high-penetrance genes such as BRCA2, STK11/LKB1, CDKN2A, PALB2, hereditary pancreatitis (PRSS1 mutation carriers), and some other known variants. Individuals could also be at high risk of PDAC due to a family history of pancreatic cancer. Approximately 10% of PDAC occurs in families with a history of PDAC. Studies have shown that when at least one pair of first degree relatives were affected with pancreatic cancer, the risk of developing pancreatic cancer was 18 times that for relatives of an individual with only one sporadic pancreatic cancer; in pancreatic cancer kindreds with three or more affected family members, there is reportedly a 57-fold increased risk of pancreatic cancer.
(2) Individuals at high risk of developing PDAC because of the presence of mucinous cysts (e.g., IPMN and MCN), and other suspected precursors such as PanIN-3. IPMNs and MCNs are being increasingly detected because of increased abdominal imaging such as CT done for diagnostic workup of non-specific symptoms. An estimated 15% of PDAC originate from these lesions, but their natural history is not well defined. Resection of IPMNs or MCNs prior to the development of invasive cancer is considered curative, but there are substantial risks of morbidity and mortality associated with surgery. Currently, it is also difficult to distinguish precancerous mucinous cysts from benign non-mucinous cysts, the timing and frequency of malignant progression within the mucinous cysts are unknown, and there is a need for biomarkers of high-grade dysplasia and risk of progression. While PanINs are not detectable using current imaging modalities, and there are also no biomarkers that can detect PanIN-3 lesions or distinguish progressor PanINs vs. non-progressors, advancement in metabolic and other molecular imaging technologies have started to show promise and potential for future clinical use.
PCDC Research Focus: The PCDC objectives include the development of biomarkers measurable in bodily fluids that can accurately and reliably detect early-stage PDAC or its lethal precursor lesions, and also distinguish progressor vs. non-progressor precursors. Although genome-wide association studies (GWAS) have reported useful findings, their utility in measuring PDAC risk is limited due to the lack of functional tests. The development of biomarker tests with high clinical sensitivity and specificity that can accurately detect progressive precursors and early-stage PDAC in non-invasively or minimally-invasively obtained biospecimens is a challenging task. High specificity is particularly important, since a positive test may trigger invasive procedures, which add their own risk of morbidity and mortality. In addition, to encourage compliance and use, the tests also need to be rapid, require a small volume of biofluids for assays, be relatively inexpensive, be widely distributable to maximize test access, and overall, have a practical approach while keeping the real-world setting in mind. Since blood or other biological fluid-based biomarkers alone may not provide sufficient tissue specificity and imaging is important for precise anatomic location and for delineating disease characteristics, the PCDC research focus includes the development of biomarkers in conjunction with imaging (radiographic, metabolic and other molecular imaging).
The PCDC follows the same biomarker development principles established by the Early Detection Research Network (EDRN), where the five phases for biomarker discovery and validation were defined as:
The PCDC also follows the EDRN-established comprehensive set of guidelines for biomarker discovery and validation studies for early cancer detection, diagnosis, and prognosis, known as the prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) study design.
The articles on the five-phase approach and PRoBE study design are available on the EDRN website (https://edrn.nci.nih.gov/about/bookshelf).
PCDC Resource Building Efforts: A major impediment to pancreatic cancer research is the limited access to well-characterized and well-annotated specimens from early stages and lethal precursors that can be used to discover and validate biomarkers. The development of extensive and efficient registries to explore novel approaches to early detection of pancreatic cancer is a necessary resource in the field. Pancreatic cancer is often diagnosed at late stages and the rapid demise of patients with PDAC contributes to the difficulty of obtaining well-annotated biospecimens. A minority of pancreatic resections are performed in a setting where tissue is routinely banked for research purposes. Even clinical centers with well-established collection protocols have very few specimens from patients with PanIN-3 and early-stage PDAC. Another shortcoming in the field is the inability of investigators to fully utilize the existing resources of individual facilities across institutions/universities. Even when registries and cohorts of patients at high risk of PDAC have been developed, they seldom have pre-diagnostic specimens and very few have serial/longitudinal samples, which hinders the much-needed progress in biomarker discovery and development for early detection. PCDC is addressing these challenges by building two longitudinal biorepositories. Samples that have already been collected under ongoing PCDC activities are in the process of being shipped to the NCI at Frederick Central Repository for long-term storage, per NCI requirement. The use of these precious samples for EDRN-defined Phase 3 biomarker validation studies will be determined following NCI-established processes. The NCI expects full commitment from the PCDC investigators towards meeting the Consortium goals and building the necessary valuable resources for the scientific community.
PCDC Signature Cohorts: This is a unique, ongoing collection of prospective, longitudinal biospecimens (blood [serum, plasma], cyst fluid, pancreatic juice) for the two types of high-risk cohorts mentioned earlier. These cohorts are called "PCDC Signature Cohorts", and collections are being accomplished through strong multi-institutional collaborations across all PCDC awardees. The collection of sufficient biospecimens that will enable the design of adequately powered, EDRN-defined Phase 3 validation studies will require continued commitment and strong collaborations among multiple institutions and participating Cancer Centers.
PCDC Reference Sets: The PCDC teams are also prospectively collecting blood samples from consented participants who have the following conditions:
These biospecimens can be designated as reference sets (EDRN-defined Phase 2, case-control sample sets) for various larger validation projects, within PCDC or with other NCI-funded consortia (e.g., EDRN).
Specific Research Areas for this FOA
This FOA is intended to support the PCDC-RUs to develop and test biomarkers and imaging methods for improved detection of early-stage PDAC and its precursor lesions, and for characterization of the precursor lesions to identify those at high risk of progression to cancer. This FOA will also support the collection of longitudinal samples (e.g., cyst fluid, serum, plasma, and other types of specimens) obtained using non-invasive or minimally invasive methods for the development of biomarkers. Prior affiliation with the PCDC is not required and all qualified investigators are invited to apply.
Examples of specific research areas include, but are not limited to, the following:
PCDC Joint Collaborative Efforts
While each funded PCDC-RU will be largely self-sufficient, the investigators will be expected to devote a portion of their effort to participate in trans-PCDC collaborative activities post-award; restricted funds will be used for these activities (see R&R Budget section) and will commence after receiving the PCDC Steering Committee (defined below) recommendation for approval. Awardees will be charged with developing collaborative projects, resources for the community, and outreach activities. All awardees will be required to interact closely with each other, engage in collaborative activities, and share resources, data, ideas and expertise that are beyond the scope of a single research team. Pancreatic cancer research requires access to samples from high-risk individuals and longitudinally collected biospecimens and images. The PCDC-RUs are expected to participate in the recruitment of high-risk patients and collect biospecimens (blood and other biofluids), both for the PCDC Signature Cohorts and for building Reference Sets (case-control), outlined earlier. For the Signature Cohorts, the PCDC-RUs will primarily follow the protocols/standard operating procedures (SOPs) and common data elements (CDEs) that have already been established by the current PCDC teams. The NCI also encourages prospective collection of pre-diagnostic images for the development of AI-based tools/methods.
PCDC Administrative and Governance Structure
The PCDC will include multiple U01 awardees (RUs) and a U24 awardee (MDCU) and will be governed by a Steering Committee. The Steering Committee will comprise of representatives from the RUs, MDCU, and the NCI. The Steering Committee will provide input towards and oversight of PCDC collaborative activities, as well as overall integration of efforts among all PCDC awardees. The Chair and the co-Chair of the Steering Committee will be PDs/PIs of PCDC cooperative agreement awards and will be elected by the Steering Committee. Any member of the Steering Committee can offer nominations for the Chair and co-Chair, including self-nominations.
Further details of Steering Committee composition and responsibilities are provided in Section VI. Award Administration Information - Cooperative Agreement Terms and Conditions of Award.
Non-responsive Applications
The following types of activities remain outside the scope of this FOA, and applications proposing them are non-responsive to this FOA and will not be reviewed.
See Section VIII. Other Information for award authorities and regulations.
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.
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.
Optional: Accepting applications that either propose or do not propose clinical trial(s).
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budget should not exceed $600,000 direct cost per year and need to reflect the actual needs of the proposed project.
The 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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
An investigator designated as a Contact PD/PI of a PCDC-RU application must not be the designated Contact PD/PI of another application under this FOA or under the companion FOA. The Contact PD/PI can be an MPI or a Co-I on another application, whether for this FOA or the companion FOA. An MPI on a PCDC-RU application may be an MPI or a Co-I on another application, whether in response to this FOA or the companion FOA.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
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.
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:
The letter of intent should be sent to:
Sudhir Srivastava, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: : 240-276-7028
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims:In addition to the specific aims, applicants should include the relevance of the research to the objectives of this FOA.
Research Strategy: Applicants must organize the Research Strategy to include the sub-section elements identified below. Applicants may include other sub-sections as needed but must include the information requested below.
Sub-section A: Overview of Research Strategy
Outline the overall theme of the proposed research, as well as the significance and innovation of the proposed studies. Propose research on the identification and testing of biomarkers measurable in bodily fluids for early detection of PDAC or its precursor lesions; determine which pancreatic cysts are likely to progress to cancer; develop molecular- and/or imaging-based approaches for screening populations at high risk of PDAC; conduct biomarker validation studies; and collect biospecimens for the establishment of biorepositories (PCDC Signature Cohorts and Reference Sets).
Define during the initial phases of development the intended clinical context in which a biomarker test will be used and the likelihood of its use in routine clinical practice, if shown to be efficacious.
For research on biomarkers, applicants are encouraged to refer to the articles on five-phase biomarker development approach (https://edrn.nci.nih.gov/about/bookshelf) mentioned earlier. This framework is used for successfully translating research on biomarker applications from the laboratory to the bedside.
Sub-section B: Research Approaches
It is essential that each PCDC-RU will identify and concentrate resources on the most promising scientific opportunities, complete studies as planned, employ sound methodologies, and where appropriate, be innovative. For each of the proposed research approaches, the following strategies should be used, wherever relevant.
Sub-section C: Study Design
The proposed study may initially involve the analysis of biospecimens from patients with neoplastic lesions vs. respective control biospecimens (case-control or cohort samples) and with adequate follow-up information. A study may involve the use of retrospectively identified and/or prospectively collected specimens. Applicants should describe in detail any proposed retrospective (existing) and/or prospective specimen collections that will be used for PCDC activities. The description should include information on the types of patients and control subjects to be accrued, clinical information to be collected, types of specimens to be collected, and quality control of the biospecimens.
Applicants must define and describe detailed eligibility criteria in reference to incidental, screening of high-risk cohorts, or symptom detected settings. If the mode of detection deviated from this, such as using a questionnaire in face-to-face interview to collect demographics and mode of detection information, applicants must describe the process. Applicants should include details on how the ascertainments were made for screen-detected or symptom-detected cases. If using retrospective cohorts, criteria for eligibility and cohort details must be provided along with detailed clinical information, such as data on follow-up, which endpoints were ascertained (cancer progression, death, cause of death) and how the endpoints were ascertained; patient age; disease stage; tumor size; lymph node status; and any other relevant diagnosis and treatment details. In situations where the specimens are being assembled from different sources and populations in terms of geography, demographics, ethnicity, etc., applicants should address the possibility of potential biases in the study design and take measures to minimize such biases.
Applicants must include a clear statement on how statistical power is defined for multiple tests and the sample size that is required to achieve this power. Examples of power definition include (a) the probability to detect at least one of possible true non-zero effects; (b) the probability to detect all non-zero effects; and (c) true discovery rate, etc. Also, in case-control designs, applicants must provide clear descriptions of whether matching is involved and what confounders are adjusted for and why.
Applicants should consider the following guidelines to avoid bias and make the best use of resources starting with the discovery process:
Sub-section D: Relevant Accomplishments
Relevant Recent Accomplishments (All Applicants): Applicants must provide, without duplicating information provided in the biosketches, a brief description of previous research experience and accomplishments relevant to the development of biomarkers and/or imaging methods for early detection of pancreatic cancer, as well as biospecimen collection.
Progress Report (Renewal Applicants Only): Include additional information in this section summarizing the current 5-year funding period and include the following items (a to d):
a) List the specific aims from previously funded application. Describe the progress made relevant to these specific aims during the current funding period and highlight the key findings for the biomarkers investigated.
b) Indicate the status of the developed markers based on the EDRN-defined biomarker development phases. What steps have been taken to advance biomarkers to Phase 2 and/or Phase 3 validation? For any unsuccessful discovery efforts, describe the alternative approaches that can be taken in the present application to be more effective. For biomarkers that have been eliminated from further investigation, briefly explain the reasons for that decision.
c) Describe the progress made on biomarker research supported through the restricted set-aside funds, if set-aside funds were used for this purpose.
d) Describe patient accrual and biospecimen contribution towards the PCDC Signature Cohorts and/or towards building the case-control Reference Sets.
Sub-section E: PCDC Collaborative Responsibilities
Building Biorepositories
Applicants should document their capabilities regarding access to patients at high risk of PDAC (e.g., familial and hereditary registries, presence of IPMN and MCN), recruit patients, procure biospecimens prospectively and longitudinally, collect epidemiological and clinical data using CDEs, protocol development, pathological assessment, biospecimen quality control, as well as the ability to process, track, store and ship specimens. Applicants are encouraged to collaborate with Cancer Centers and/or cooperative groups for any appropriate ongoing trials and/or surveillance cohorts for access to suitable patient populations and any unique opportunity for prospective longitudinal collection of specimens. Applicants must also demonstrate a sincere effort toward inclusion of minority and underserved populations.
Applicants should also document their ability to collect cross-sectional biospecimens from sporadic cases of early-stage PDAC (stages IA, IB, IIA, and IIB) and any other histological type, pancreatic cancer precursor lesions (PanINs), cystic lesions (IPMNs and MCNs), and benign pancreatic conditions (e.g., chronic pancreatitis, biliary obstruction). Types of biospecimens to be collected may include plasma, serum, buffy coat, DNA, stool, urine, pancreatic juice, cyst fluid, diagnostic tissue biopsies, pancreatic resections, image-guided proximal samples (e.g., EUS guided). Applicants with the ability to collect autopsy samples (precursor and early-stage cases) should include procedures for acquiring samples and obtain/submit clearances from State and regulatory authorities, including those from an institutional review board (IRB).
Applicants should describe plans for depositing a portion of the samples collected during the tenure of this funding in the NCI at Frederick Central Repository for building the PCDC Signature Cohorts and the Reference Sets (cases and controls) described earlier. The PCDC-RUs are expected to coordinate with the PCDC-MDCU for trans-PCDC collaborative projects, protocol development, statistical analyses, biospecimen blinding, biospecimen data deposition supported by the PCDC-MDCU, and for tracking, shipping, and storing biospecimens at the NCI at Frederick Central Repository. New applicants must note that biospecimen collection for the PCDC Signature Cohorts will be mainly based on the SOPs and CDEs already established by the current PCDC and approved by the Steering Committee.
For new and incumbent applicants, the PCDC Signature Cohort project will be developed and renewed, respectively, post-award, and restricted/set-aside funds will be used towards this activity, as mentioned earlier. Activities will commence after receiving approval from the Steering Committee and restriction being lifted by the NCI.
Other Joint Collaborative Activities
Sub-section F: Annual Milestones
The following major benchmarks of progress must be addressed. Any application lacking milestones will be considered incomplete.
Applicants should provide a clear set of annual, quantitative benchmarks for each specific aim of the PCDC-RU associated with timelines.
These milestones must be well described, quantitative, and scientifically justified. Discuss the milestones as a means for judging the success of the proposed studies. Specific aims may not be regarded as milestones (unless they include quantitative endpoints). The specific aims describe the goals and intended path of the proposed research. Quantitative milestones are a way of determining whether an applicant has successfully reached the specified goals. Applicants are expected to provide milestones for each specific aim. Milestones should be clearly stated and presented in a quantitative manner, such as numerical specifications of sensitivity and specificity, or a count of some newly discovered molecules or molecular pattern(s) that can be used as biomarkers for early detection of PDAC or risk assessment of its lethal precursors.
Examples of quantitative milestones are:
Letters of Support: In addition to standard items, applicants must provide letters from the respective leadership official(s) in the institution(s) documenting specific institutional commitments for the PCDC-RU. Letters should also be included that reflect any additional resources and partnerships (e.g., for-profit sector, industry, large cohorts) that will be employed to achieve the goals of the PCDC-RU. Please also provide letters from collaborators documenting access to appropriate samples.
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.
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.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit 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 NCI. Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
In addition, for applications involving clinical trials: A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is 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?
In addition, for applications involving clinical trials
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the 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?
In addition, for applications involving clinical trials
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
In addition, for applications involving clinical trials
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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: If the proposed study is a biomarker validation study, how well does it incorporate principles of the PRoBE (or a similar) study design? How feasible and appropriate are the strategy and available resources for longitudinal collection of biospecimens?
In addition, for applications involving clinical trials
Does the application adequately address the following, if applicable
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
In addition, for applications involving clinical trials
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
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.
Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. 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:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the 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.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
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.
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, 2 CFR Part 200, 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 recipients 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 for the project as a whole resides with the recipients, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
The PDs/PIs will have primary responsibility for:
Recipients 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.
NCI Program Officials have substantial programmatic involvement that is above and beyond the normal stewardship role in cooperative agreement awards. The substantially involved NCI Program Official, acting as Project Coordinator, will coordinate in a centralized fashion the various activities of the recipients. Additionally, an NCI Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Additional Program Officials who are not responsible for the normal scientific and programmatic stewardship of the award may be designated as Project Scientists and assist in Consortium activities. Specific responsibilities of the NCI Program Officials will include, but will not be limited to, the following aspects:
The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to those Consortium recipient institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance.
Areas of joint responsibility include:
Steering Committee: The Steering Committee will be the main governing body for the PCDC. The Steering Committee will be composed of the following voting members:
Each voting member will have one vote.
Additional NIH staff may participate in Steering Committee meetings as non-voting members as needed (for example to provide additional expertise). The non-voting members may include representatives from NCI extramural divisions and a representative from the NCI CBIIT.
Additional non-voting members may participate on the Steering Committee in an advisory capacity on an as needed basis and decided by the existing voting committee members.
The Chair of the Steering Committee (who cannot be an NIH staff) will be selected by the Steering Committee.
The Steering Committee will meet twice every year, at locations selected by the Steering Committee in consultation with the NCI; one in-person meeting and one virtual meeting.
The Steering Committee may establish working groups for specific purposes. The NCI Project Coordinator/Scientist(s) and Program Officials will serve on such working groups, as appropriate.
Primary responsibilities of the Steering Committee include, but are not limited to, the following activities:
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 recipient. This special dispute resolution procedure does not alter the recipient'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.
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
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.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Sudhir Srivastava, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7028
Email: [email protected]
Matthew Young, Ph.D.
National Cancer Institute (NCI)
Telephone:240-276-5846
Email: [email protected]
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]
Amy R. Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6375
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 2 CFR Part 200, 42 CFR Part 52 and 45 CFR Part 75.