PAR-28-056-Full-Announcement.html

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)

Note: Not all NIH Institutes, Centers, and Offices (ICOs) participate in Announcements. Applicants should carefully note which ICOs participate in this announcement and view their respective areas of research interest at the ICO-Specific Scientific Interests website. ICOs that do not participate in this announcement will not consider applications for funding.

Funding Opportunity Title

Pancreatic Cancer Detection Consortium: Research Units (U01 Clinical Trial Optional)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of

PAR-21-334

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

PAR-28-056

Companion Funding Opportunity

PAR-28-057

, U24 Resource-Related Research Project (Cooperative Agreements)

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.393

Funding Opportunity Purpose

Through this Notice of Funding Opportunity (NOFO), NCI solicits 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 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 patients at high risk of PDAC (because of genetic factors, family history and/or the 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 lesions 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.

Funding Opportunity Goal(s)

To identify cancer risks and risk reduction strategies, to identify factors that cause cancer in humans, and to discover and develop mechanisms for cancer prevention and preventive interventions in humans.

Key Dates

Posted Date

September 25, 2026

Open Date (Earliest Submission Date)

January 05, 2027

The following table includes NIH standard due dates marked with an asterisk.

February 05, 2027 *

March 05, 2027 *

Not Applicable

December 2027

June 05, 2027 *

July 05, 2027 *

Not Applicable

April 2028

October 05, 2027 *

November 05, 2027 *

Not Applicable

July 2028

February 05, 2028 *

March 05, 2028 *

Not Applicable

December 2028

June 05, 2028 *

July 05, 2028 *

Not Applicable

April 2029

October 05, 2028 *

November 05, 2028 *

Not Applicable

July 2029

February 05, 2029 *

March 05, 2029 *

Not Applicable

December 2029

June 05, 2029 *

July 05, 2029 *

Not Applicable

April 2030

October 05, 2029 *

November 05, 2029 *

Not Applicable

July 2030

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

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

Due Dates for E.O. 12372

Not Applicable

Expiration Date

November 06, 2029

Required Application Instructions

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

Conformance to all requirements (both in the Application Guide and the NOFO) 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.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

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. However, early detection significantly improves survival outcomes. Surgical resection remains the only potentially curative treatment, but only approximately 20% of patients are eligible for surgery at diagnosis. Even among those who undergo surgery, the recurrence rate is still high.

PCDC was initiated as a consequence of the Recalcitrant Cancer Research Act of 2012 and the NCI 2014 Scientific Framework for Pancreatic Ductal Adenocarcinoma. Pancreatic cancer has a 5-year relative survival rate of 13.3%, with an estimated 67,440 new cases, and 51,980 deaths in the United States in 2025 (SEER) 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 may be 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. Evidence suggests 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.

Liquid biopsy approaches specific to PDAC, including assays based on ctDNA, methylation signatures, exosomal RNA, and protein biomarkers are actively being explored by PCDC for biomarkers that will predict progression of pre-cancer lesions and/or detect early stage PDAC in high risk populations. PCDC is also integrating imaging approaches with liquid biopsies for PDAC detection. However, there remains a need for the development and validation of better molecular, imaging and/or integrated molecular and imaging approaches that are highly discriminating for pancreatic cancer and clinically useful.

Biomarker Definition. In the context of this NOFO, 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.

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). For surveillance imaging protocols include 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 limited sensitivity for detecting very early pancreatic cancer and its microscopic precursor lesions. The consortium is developing several clinically useful screening markers that 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. PCDC is also working with the Early Detection Research Network (EDRN) and the Alliance of Pancreatic Cancer Consortia (APaCC) to develop a repository of pre-cancer images that are available for developing and validating artificial intelligence (AI)-based algorithms to identify pre-cancer in CT scans.

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 include high-penetrance genes (such as BRCA2, STK11/LKB1, CDKN2A, PALB2), hereditary pancreatitis (PRSS1 mutation carriers), and 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.

(2) Individuals at high risk of developing PDAC because of the presence of mucinous cyst lesions (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. Advancements in metabolic and other molecular imaging technologies have started to show promise and potential for future clinical use.

Multi-cancer detection (MCD) tests are blood-based assays designed to identify multiple cancers at early, more treatable stages by detecting tumor-derived signals such as ctDNA, DNA methylation patterns, and protein biomarkers using similar technology that PCDC is using for PDAC detection. Key challenges for MCDs include the inability to detect preinvasive lesions and early stage PDAC. PCDC is focused on developing and validating more sensitive assays that could be useful for screening MCD test positive patients.

PCDC Research Focus: The PCDC objectives include the development of tests with high clinical sensitivity and specificity that can accurately detect progressive precursors and early-stage PDAC in noninvasively or minimally invasively obtained biospecimens. High specificity for these tests is particularly important, since a positive test may trigger invasive procedures. In addition, these tests must be rapid, cost-effective, widely distributable, and designed with practical in real-world settings. Since biomarkers alone may not provide sufficient tissue specificity. The PCDC research focus includes the development of biomarkers in conjunction with imaging modalities (including radiographic, metabolic and molecular imaging techniques).

The PCDC follows the same biomarker development principles established by the EDRN, where the five phases for biomarker discovery and validation were defined as:

The articles on the five-phase approach and PRoBE study design are available on the EDRN website.

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, which are critical for biomarker discovery and validation. PCDC has initiated the establishment of comprehensive, longitudinal registries and biorepositories, a necessary and foundational step toward advancing early detection strategies. Pancreatic cancer is often diagnosed at late stages and the rapid progression and high mortality of PDAC make it difficult to obtain high-quality biospecimens, particularly from early-stage patients. Another shortcoming in the field is the inability of investigators to fully utilize the existing resources of individual facilities across institutions, which limits collaboration and reduces the efficiency of existing efforts. Registries and cohorts of patients at high risk of PDAC seldom have pre-diagnostic specimens and very few have serial/longitudinal samples, which are essential for identifying dynamic biomarkers that reflect disease initiation and progression.

PCDC is addressing these challenges by building two integrated, longitudinal biorepositories. Samples that have already been collected under ongoing PCDC activities are being shipped to a Central Repository for long-term storage. The use of these precious samples for EDRN-defined Phase 3 biomarker validation studies will follow established consortium and NCI review and access processes. The full engagement and collaboration from PCDC investigators in building these shared resources, which are critical for achieving the Consortium's goals and accelerating progress in early detection research for the broader scientific community is required.

PCDC Prospective Cohorts: This is a unique, ongoing collection of prospective, longitudinal biospecimens including blood [serum, plasma], cyst fluid, and pancreatic juice from the types of high-risk populations previously described. These cohorts known as "PCDC Prospective Cohorts", are being developed through strong multi-institutional collaborations across all PCDC grant recipients. 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 are designated as reference sets for various larger validation projects, within PCDC or with other NCI-funded consortia.

Applications Not Responsive to this NOFO The following types of studies are not responsive to this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed or considered for funding:

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance 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 NOFO.

Application Types Allowed

New

Renewal

Resubmission

Revision

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budget should not exceed $600K direct costs per year and need to reflect the actual needs of the proposed project.

Award Project Period

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 NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

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

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 not allowed.

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

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. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

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.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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 their organization to develop an application for 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 How to Apply-Application Guide.

An investigator designated as a Contact PD/PI or MPI for a PCDC-RU application must not be the designated Contact PD/PI or MPI of another application under this NOFO, under the companion U24 NOFO, PAR-28-057 or any currently funded RUs.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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.

Page Limitations All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

SF424(R&R) Senior/Key Person Profile

R&R or Modular Budget

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: In addition to the specific aims, applicants must include the relevance of the research to the objectives of this NOFO.

Research Strategy: Applicants must organize the Research Strategy to include the sub-section elements identified below. Applicants may include other sub-sections as needed.

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 bio-repositories (PCDC Prospective 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 incorporate the five-phase biomarker development approach. This approach 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 identifies and concentrates resources on the most promising scientific opportunities, completes studies as planned, employs sound methodologies, and, where appropriate, be innovative. The proposed research approach must include one or more of the following strategies.

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 must describe in detail any proposed retrospective (existing) and/or prospective specimen collections that will be used for PCDC collaborative activities. The description must 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 there is a deviation from this mode of detection , such as using a questionnaire in a face-to-face interview to collect demographics and mode of detection information, applicants must describe the process. Applicants must include details of 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, etc., applicants must 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) the 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:

Applicants must describe the infrastructure for data storage, data security and data analysis.

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): Applicants must 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. Inclued the steps 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 Prospective Cohorts and/or towards building the case-control Reference Sets.

Sub-section E: PCDC Collaborative Responsibilities Building Biorepositories Applicants must document their capabilities regarding access to patients at high risk of PDAC (e.g., familial and hereditary registries, presence of IPMN and MCN), recruitment of patients, procurement of biospecimens prospectively and longitudinally, collection of 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 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 must 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 Prospective 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 Prospective Cohorts will be mainly based on the SOPs and CDEs already established by the current PCDC and approved by the Steering Committee.

Joint Collaborative 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. For the Prospective Cohorts, the RUs are required to follow the protocols/standard operating procedures (SOPs) and common data elements (CDEs) that have already been established by the current PCDC teams. Funding could be delayed if institutes are not able to agree to these requirements. The NCI also encourages prospective collection of pre-diagnostic images for the development of AI-based tools/methods.

Investigators are required 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 in year 2 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. Applicants should provide plans for working collaboratively with the other PCDC-RUs and the PCDC-MDCU to facilitate the discovery, clinical validation, and clinical application of biomarkers through participation in multi-institutional studies. Applicants should describe their expertise in data quality control, analysis, and interpretation of results for validation studies if they have previously participated in validation studies.

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 How to Apply - Application Guide.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.

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 How to Apply- 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

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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply – 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…