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

Pancreatic Cancer Detection Consortium: Research Units (U01 Clinical Trial Optional) is sponsored by National Cancer Institute (NCI). This Notice of Funding Opportunity (NOFO) from the NCI solicits applications for Research Units (RUs) to conduct research on the early detection of pancreatic ductal adenocarcinoma (PDAC) and the characterization of its precursor lesions.

Expired PAR-21-334: Pancreatic Cancer Detection Consortium: Research Units (U01 Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) f National Institutes of Health ( NIH ) Components of Participating Organizations National Cancer Institute ( NCI ) Funding Opportunity Title Pancreatic Cancer Detection Consortium: Research Units (U01 Clinical Trial Optional) U01 Research Project Cooperative Agreements NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available.

See Notice NOT-OD-22-018 . September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022.

August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170 April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity Resource-Related Research Project (Cooperative Agreements) See Section III.

3. Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity 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 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.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to application due date. Renewal / Resubmission / Revision (as allowed) 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.

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

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

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.

Funding Opportunity Description 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. 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: Phase 1: The preclinical exploratory phase; Phase 2: The clinical assay validation phase (case-control); Phase 3: The retrospective longitudinal validation phase; Phase 4: The prospective screening phase; and Phase 5: The cancer control phase.

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: Develop and validate new blood- or other bodily fluid- and tissue-related biomarkers (e.g., genomic, proteomic, epigenomic, metabolomic, glycomic) using deep 'omic' profiling technologies to detect early-stage PDAC and precursor lesions (e.g., high-grade IPMN and MCN) that could be used to select patients for surgical intervention; Develop precise and sensitive imaging methods to detect early-stage PDAC and high-grade precursors (e.g., PanIN-3) that could be used to select patients for surgical intervention (imaging modalities can be anatomical, functional, or molecular); Develop and integrate imaging approaches with multiplex biomarker panels; Develop imageable biomarkers for anatomic localization of PDAC and high-grade precursor lesions (e.g., PanIN-3); Utilize existing knowledge gained from large cohort studies and GWAS in pancreatic cancer, and develop robust data science-based biomarker discovery/development (in silico) research project; Develop artificial intelligence (AI)/deep learning (DL)/machine learning language (MLL)-based algorithms to aid in the development and refinement of early detection and risk stratification approaches; Develop risk prediction models based on clinical and molecular information; Evaluate longitudinal screening protocols in patients at high risk of developing pancreatic cancer; Conduct longitudinal collection of biospecimens and images from patients with pancreatic cysts to determine which ones are likely to progress to PDAC within a defined period (e.g., 3 years); determination of cysts with high malignant potential that are resectable; and Develop novel methods to obtain and interrogate pancreas biospecimens that may indicate the presence of early cancer (e.g., obtain more pure pancreatic juice, study duct cancerization).

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.

This FOA will not support research on new genome-wide association studies (GWAS), mechanistic studies, such as studies on growth regulation, cell cycle control, or other basic studies, which are not explicitly focused on detection of early-stage PDAC or risk assessment of its precursor lesions in humans. The FOA will also not support studies focused exclusively on in silico approaches and/or risk prediction models.

Studies based exclusively on preclinical models (e.g., mouse, organoid) are not acceptable , and all studies must include human subjects. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for this FOA. Application Types Allowed 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?

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. 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. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession 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 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 must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.

gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants.

gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants. gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

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

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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. 3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

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

Application and Submission Information 1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution.

Links to apply using ASSIST or Grants. gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. 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