Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

Imaging, Biomarkers and Digital Pathomics for the Early Detection of Premetastatic Aggressive Cancer (R01 Clinical Trial Optional)

Activity Code

R01 Research Project Grant

Announcement Type

Reissue of PAR-16-089

Related Notices

None

Funding Opportunity Announcement (FOA) Number

PAR-19-264

Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.393; 93.394

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) will support the development of state-of-the-art projects that include imaging, biomarkers, digital pathomic and other -omic integration strategies for improving current approaches for the earliest detection of premetastatic aggressive cancer as well as identifying precancerous lesions that will subsequently demonstrate an aggressive phenotype. This FOA specifically attempts to address and improve diagnostic uncertainty in clinical decisions in a technology agnostic manner by improving sensitivity and specificity of applied tests. N-dimensional co-registered, cross-correlated imaging results integrated with multiplexed biomarker data and digital pathomics using analytic strategies such as artificial intelligence and virtual reality visualization for improving discovery are encouraged. The projects supported by this FOA will collectively participate in the existing Consortium for Imaging and Biomarkers (CIB) Research Program. The goals of the CIB are to: (1) improve diagnostic performance by developing methodology for the early identification of lethal cancer versus non-lethal disease, (2) to minimize/better manage overdiagnosis and (3) to reduce false positives and false negatives.

Key Dates
Posted Date

May 1, 2019

Open Date (Earliest Submission Date)

June 10, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

July 10, 2019; December 10, 2019; July 10, 2020; December 10, 2020; July 9, 2021; December 10, 2021, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

September/October 2019; March/April 2020; September/October 2020; March/April 2021

Advisory Council Review

January 2020; August 2020; January 2021; August 2021; January 2022; August 2022

Earliest Start Date

February 2020; October 2020; February 2021; October 2021; February 2022; October 2022

Expiration Date

December 11, 2021

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the 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
    Purpose

    This Funding Opportunity Announcement (FOA) will support the development of state-of-the-art projects that include imaging, biomarkers, digital pathomics and other -omic integration strategies for improving current approaches for the earliest detection of premetastatic aggressive cancer as well as identifying precancerous lesions that will subsequently demonstrate an aggressive phenotype. This FOA specifically attempts to address and improve diagnostic uncertainty in clinical decisions in a technology agnostic manner by improving sensitivity and specificity of applied tests. N-dimensional co-registered, cross-correlated imaging data integrated with multiplexed biomarker results and digital pathomics using analytic strategies such as artificial intelligence and virtual reality visualization for improving cancer research discovery are encouraged.

    The projects supported by this FOA will collectively participate in the existing Consortium for Imaging and Biomarkers (CIB) Research Program. The goals of the CIB are to: (1) improve diagnostic performance by developing methodology for the early identification of lethal cancer versus non-lethal disease, (2) to minimize/better manage overdiagnosis and (3) to reduce false positives and false negatives.

    This FOA will utilize the NIH Research Project Grant (R01) mechanism and is suitable for projects where proof-of-principle of the proposed methodology has already been established and supportive preliminary data are available. 

    Background and Rationale

    Clinical Needs:

    Overdiagnosis and false positives present significant clinical problems in the prevention, detection and treatment of cancer. Therefore, there is an unmet clinical need to more accurately identify early-stage aggressive cancers and distinguish lesions that are life threatening from those that are not.

    The specific objective of this FOA is to stimulate and support cancer imaging, biomarkers, digital pathomics and other -omic research to develop, optimize, and clinically validate novel methods to:

    • Detect aggressive cancers at the earliest stages possible;
    • Reduce overdiagnosis;
    • Reduce false positive tests; and
    • Identify lethal cancers from non-lethal disease.

    While early stage cancers that were heretofore undetectable can now be detected by screening, many lesions detected by imaging or biomarkers are not cancer and many of the detected cancers are not life threatening. Simply stated, although it is possible to detect early stage cancers with greater frequency, one does not always know which lesions are cancerous and cannot always distinguish cancers that are life threatening from those that are not. Overdiagnosis is the term used when the diagnosis of a disease is correctly made, but the disease does not give rise to symptoms during the patient's lifetime nor have lethal potential for the patient. False positive is the term used when the test for disease in a patient is "positive" when the disease is not present. Our inability to differentiate lethal from indolent cancer (frequently over diagnosed), particularly at an early stage, and to differentiate benign disease from cancer (false positives) is a significant clinical problem.

    The goal of this FOA is to develop improved methods for the early detection of aggressive cancer by managing overdiagnosis, reducing false positives and identifying lethal cancers from non-lethal disease using strategies aimed at effective integration and validation of imaging, biomarkers, pathomics and other -omic data. It is acknowledged that a biomarker is conceptually defined as a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes or a biological response that could be used for early cancer detection. While imaging and biomarkers can both be derived from tissue, cancer cells, serum, plasma, urine or other bodily fluids, for the purpose of this FOA, a biomarker will specifically refer to results obtained from the analysis of biofluids and tissues that are not spatially or temporally resolved.

    Likewise, imaging is referred to as a “tool” used to graphically depict spatially, functionally or temporally resolved cancer cells, tissues and their surroundings. In the context of this FOA, imaging can employ any of a variety of radiographic, sonographic, and other diagnostic technologies. Imaging and biomarker tests used in this fashion are generally obtained separately and then integrated as a function of time. An imageable biomarker, for the purpose of this FOA, combines structural, functional and/or temporal information from one or more dynamic biomarker(s) or image features that can be mapped and visualized.

    Generally, imageable biomarker results are obtained simultaneously (rather than serially) and are comprised of data originating from a complex combination of cancer cells, cellular features, molecular analytes, or image derived features (genomic, proteomics, metabolomics, or other -omics data including radiomic and pathomic features) that may or may not be directly mapped for quantitative visualization, but are nonetheless associated with and derived from image-based acquisitions. Data obtained in this manner correlate to disease processes and aberrant metabolic pathways that can be applied clinically in the context of precision medicine. The following three examples are provided as illustrations of possible approaches that are responsive to this FOA:

    EXAMPLE #1: Validated Biomarker(s) + Investigational Imaging Approach

    Prostate Cancer: Aberrant biomarker results trigger subsequent imaging: Currently, prostate specific antigen (PSA) is used to screen men for prostate cancer, but the rates of both overdiagnosis and false positives are unacceptably high. The biomarker prostate cancer antigen-3 (PCA3) has recently been approved by the FDA as a urine test for predicting prostate cancer on second biopsy. The FDA has also recently approved pro prostate specific antigen (proPSA) as a serum biomarker for prostate cancer. While these biomarkers are superior to PSA alone, the number of false positive and extent of overdiagnosis are still too high. The successful integration and validation of imaging and biomarker approaches might be used to help guide and better define criteria used for clinical decisions. The need for better molecular, pathomic, genetic, and imaging predictive markers as well as the evaluation of their validity and reliability is critical for advancing our understanding the natural history of prostate cancer, for establishing guidelines to be used for clinical decisions and active surveillance in the management of men with localized prostate cancer and for managing overdiagnosis. A specific example for combining a known biomarker with an investigational imaging method is when screening results from a validated biomarker are abnormal and consistent with prostate cancer. Subsequent biopsy of the prostate suggests a low to moderate grade cancer (Gleason grade 3-5). A clinical decision regarding treatment or active surveillance subsequently needs to be made. In such cases, the application of a functional imaging test that could more accurately determine cancer extent and assess cancer aggressiveness would be significant.

    EXAMPLE #2: Established Diagnostic Imaging + Investigational Biomarker(s) Approach

    Lung Cancer: Indeterminate lesion(s) on imaging triggers subsequent biomarker study: The results from the National Lung Screening Trial (NLST) of high-risk current and former smokers found that low-dose helical computed tomography (CT) decreased lung cancer mortality by 20%. Data from the NLST suggest that a reduction in mortality of more than 23,000 patients per year could be achieved by population screening for lung cancer in people who currently use tobacco. However, 25% of the subjects in the CT arm of NLST demonstrated abnormalities and 95% of those lesions  were determined to be false-positives. Lesions thought to be malignant on imaging often require additional diagnostic procedures resulting in increased radiation exposure, needle biopsy or other invasive procedures such as thoracotomy. Potentially serious complications can result from these procedures and delay treatment of aggressive cancer. While diagnostic imaging-based strategies to address this problem are ongoing, many questions remain given the high false positive rate of CT. The ability to better stratify patients at risk and to determine which CT or X-ray detected lung nodules truly represent aggressive lung cancer in a safe, cost effective manner could facilitate early treatment and thereby improve lung cancer outcomes while minimizing complications from diagnostic procedures performed on patients without lung cancer. A specific example for combining a known imaging method with an investigational biomarker is that after a positive CT for lung cancer, a biomarker or panel biomarkers with very high sensitivity for cancer and even modest specificity (high negative predictive value) could be subsequently used to eliminate a large fraction of false positive nodules and unnecessary follow up procedures.

    EXAMPLE #3: Imageable Biomarker + Clinical Diagnostic Standard-of-Care Imaging with Established Gold Standard for Use in Multi-Site Verification and Pre-Validation Studies

    Pancreatic Cancer: As one possible example, pancreatic cancer, is herein provided as context for the use of an imageable biomarker. Briefly, the poor prognosis of Pancreatic Ductal Adenocarcinoma (PDAC) is primarily due to its advanced stage at diagnosis. Pancreatic cancer does not exhibit early symptoms, and symptoms, when they do occur, are often nonspecific. Consequently, patients often present with locally advanced or metastatic disease. Surgical resection is currently the only potentially curative treatment, but it is only possible for 15-20% of patients, and most patients who undergo surgical resection will have disease recurrence. Studies suggest an average of approximately 17 years between the occurrence of the initiating mutation and the acquisition of metastatic potential in PDAC. This window of time may offer an opportunity for curative interventions if the disease could be diagnosed at an earlier stage. Most imaging strategies for pancreatic cancer include invasive studies such as endoscopic retrograde cholangiopancreatography or endoscopic ultrasound (EUS). Having a safe, highly discriminatory, noninvasive tool to detect PDAC would provide a mechanism for these patients to be screened safely and effectively, with the hope of decreasing mortality from PDAC through early detection.

    Currently available modalities for pancreatic cancer screening are mostly anatomical, including traditional cross-sectional imaging such as abdominal ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI), and invasive imaging such as EUS. Traditional cross-sectional imaging has little role in screening for sporadic pancreatic cancer. However, there have been significant advances in biomedical imaging and related physiologic based technologies that may allow for the detection of pancreatic intraepithelial neoplasia (PanIN-3) and early stage PDAC. For example, quantitative EUS elastography and microbubble contrast-enhanced EUS, which allow better visualization and delineation of focal pancreatic lesions might be of benefit. Patients with intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are at high risk of developing PDAC. IPMNs and MCNs can be detected by abdominal imaging because they produce radiographically identifiable ductal dilatation and have been increasingly identified using abdominal imaging such as CT done for workup of nonspecific symptoms. However, the natural history of these lesions is not well defined.

    An estimated 15% of PDAC originate from these lesions. One-third of IPMNs are associated with an invasive carcinoma, and at the time of diagnosis, there is a 40% to 50% chance of the IPMN already being cancerous. MCNs are large mucin-producing precancerous lesions that are less common than IPMNs. MCNs can progress to PDAC, and one-third of patients with resected MCNs have cancer. 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 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 accurate biomarkers, imaging protocols and the development of imageable biomarkers to identify high-grade dysplasia and risk of progression.

    Specific Research Objectives

    This FOA will support collaborative research focused on the integration of imaging, biomarker(s) and digital pathomic data applied specifically toward improving current clinical methods used for cancer screening, early detection of aggressive cancer, assessment of cancer risk and differential diagnosis.

    These goals can be met by a research strategy involving preclinical and clinical investigations to improve early cancer detection and clinical management decisions where validated cancer biomarkers can be combined with experimental imaging methods, or conversely, where established clinical imaging methods can be combined with experimental biomarkers.

    It is also possible that experimental imaging and biomarker integration strategies may be combined in such a manner that a clear path to clinical application is maintained. For example, clinically established imaging approaches or validated multiplexed biomarker tests may not be currently available, well defined and suitable for direct incorporation into multi-site validation studies, i.e., experimental imaging combined with experimental biomarker(s) or the development of novel imageable biomarkers. For grant applications involving such a strategy, an established reference standard or gold standard (e.g., histology or immunohistochemistry) is required and should be clearly defined within the grant application in order to perform ongoing or future verification, prevalidation and clinical validation studies.

    Because of the multidisciplinary nature of the FOA, applicants are encouraged to take advantage of the option to designate multiple Program Directors/Principal Investigators (PDs/PIs), each of whom would contribute unique expertise and scientific insights toward the successful completion of the proposed research. N-dimensional co-registered, cross-correlated imaging data integrated with multiplexed biomarker results and digital pathomics using analytic strategies such as artificial intelligence and virtual reality visualization for improving cancer research discovery are encouraged whenever possible.

    Scientific Areas Appropriate for Applications under this FOA

    Applicable clinical research could include, but not be limited to, the following:

    • Use of molecular diagnostic tests to evaluate lesions observed by imaging and biomarker(s) to distinguish aggressive from indolent cancer or benign lesions from cancer.
    • Use of imaging to evaluate biomarker results to improve sensitivity and specificity for early detection and differential diagnosis.
    • Correlation of imaging with genomic results (radiogenomics) or other omics results, such as the rich TCGA and proteomic databases.
    • Development and combined use of imaging and biomarker(s) that could improve current standards-of-care for screening, early detection of aggressive cancer, assessment of risk, differential diagnosis and clinical management decisions.

    Appropriate strategies used to optimize the performance of imaging and biomarker approaches for ultimate clinical validation include:

    • Leveraging advances in novel imaging methods that can be performed on different platforms and across wide resolution scales from the molecular, cellular and organ level either by external tomography, localized detectors or implanted devices in vivo or as applied to laboratory methods;
    • Leveraging advances in novel multi-parametric biomarker detection technologies and approaches including genomics, proteomics, epigenomics, metabolomics, radiogenomics, and digital pathomic approaches;
    • The development of informatics resources to help optimize the above strategies and support sharing of data and validation methods to promote more standardized approaches for data integration, visualization and clinical management decisions.

    The optimization, application and validation of emerging imaging or biomarker approaches targeted specifically for clinical application are appropriate and can include:

    • Novel imaging probes or contrast (enhancing) agents applied to established, commercially available imaging instrumentation would be considered if used to answer a well-defined clinically significant question, and, quantitative reference standards are used for verification and validation.

    Customized imaging probes or approaches incorporated into commercially available imaging instrumentation that might be acceptable include, but not limited to: positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, Dynamic Nuclear Polarization (DNP) MR chemical shift imaging (CSI), computed tomography (CT), ultrasound (US), photo acoustic imaging (PAI) and photonic based approaches as well as number of developing technologies such as Multiplexed Ion Beam Imaging (MIBI), imaging mass cytometry, MALDI imaging mass spectrometry (MALDI-IMS), laser ablation system spectrometer (CyTOF) and pathomic based techniques and analytics.

    NCI has a rich history of support for collaborative networks, resources, archives and biorepositories including, but not limited to:

    and/or

    Related public resources such as:

    and

    While there is no requirement that investigators submitting applications to this FOA incorporate existing NCI collaborative networks, resources, archives or biorepositories into their experimental design, it is expected that the research funded through this FOA will take advantage of, whenever possible and appropriate, currently available NCI resources, expertise and collaborations.

    It is also expected that the research funded through this FOA will take advantage of, whenever possible and appropriate, recalcitrant and rare cancers including but not limited to the detection of early stage pancreatic, lung, brain, esophageal, liver, ovarian, head and neck and stomach cancers as well as precancerous lesions.

    PD/PI’s are also encouraged to take advantage of, whenever possible and appropriate, developing and novel applications of analytics and technologies involving artificial intelligence (AI), computer assisted diagnostics (CAD), virtual reality (VR) and N-dimensional visualization methods for understanding and elucidating interactive relationships in complex data sets. 

    Whenever possible, research should address and develop detailed co-registration approaches for cross-correlated data originating from diverse platforms and spatial, functional and temporal resolutions typically used for imaging, biomarkers and other omic sources. For example, the incorporation of fiduciary markers or physiologic landmarks for feature registration over large dynamic ranges in a google-maps like approach is desirable.

    Consortium for Imaging and Biomarkers (CIB)

    All newly funded independent R01 scientific research projects will be included in the current CIB program (currently composed of U01s and R01s). Although separate research projects will be funded by individual R01 awards and will operate independently, separate research projects will be encouraged to interact closely and leverage the expertise of other CIB awardees, engage in collaborative activities, and share resources, ideas and expertise beyond the scope of their individual research team. The CIB membership at-large will: determine guidance and policy decisions, manage and coordinate webinars, annual meetings, dissemination of information, oversee integration of collaborative efforts among the awardees and all collaborative activities. CIB meetings will provide a venue for presenting scientific findings from each of the funded studies and are intended to facilitate synergistic interactions among the projects within the evolving community of scientists. The investigators may form committees that would meet periodically by conference calls as needed. PDs/PIs will be expected to participate in these conference calls at monthly or other appropriate intervals. Other investigators should set time aside as needed to participate in cross-cutting "research interest groups" and other collaborative activities as a way of advancing transdisciplinary science.

    Research Projects that are NOT Appropriate for this FOA

    This FOA will NOT support the development of new imaging technology or approaches aimed solely for biomarker discovery.

    This FOA is unique compared to other FOA's in that it specifically focuses on facilitating multidisciplinary collaboration of experts from the imaging and biomarker research communities for the sole purpose of developing integrative imaging and biomarker(s) protocols with pathomic correlation or co-registration methods for: (1) developing methodology for the early identification of lethal cancer versus non-lethal disease, (2) minimize/better manage overdiagnosis and (3) reduce false positives and false negatives.

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

    Section II. Award Information
    Funding Instrument

    Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

    Application Types Allowed

    New
    Renewal
    Resubmission
    Revision

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    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 budgets are not limited but need to reflect the actual needs of the proposed project.

    Award Project Period

    The maximum project period is 5 years. The scope of the proposed project should determine the project period.   

    NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Higher Education Institutions

    • Public/State Controlled Institutions of Higher Education
    • Private Institutions of Higher Education

    The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

    • Hispanic-serving Institutions
    • Historically Black Colleges and Universities (HBCUs)
    • Tribally Controlled Colleges and Universities (TCCUs)
    • Alaska Native and Native Hawaiian Serving Institutions
    • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

    • State Governments
    • County Governments
    • City or Township Governments
    • Special District Governments
    • Indian/Native American Tribal Governments (Federally Recognized)
    • Indian/Native American Tribal Governments (Other than Federally Recognized)
    • Eligible Agencies of the Federal Government
    • U.S. Territory or Possession

    Other

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

    Non-domestic (non-U.S.) Entities (Foreign Institutions) are   eligible to apply.
    Non-domestic (non-U.S.) components of U.S. Organizations are   eligible to apply.
    Foreign components, as defined in the NIH Grants Policy Statement, are   allowed.

    Required Registrations

    Applicant Organizations

    Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM)– Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • 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.

    2. Cost Sharing

    This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

    3. Additional Information on Eligibility
    Number of Applications

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

    The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

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

    The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

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

    Letter of Intent

    Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

    By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

    • Descriptive title of proposed activity
    • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
    • Names of other key personnel
    • Participating institution(s)
    • Number and title of this funding opportunity

    The letter of intent should be sent to:

    Richard Mazurchuk, Ph.D.
    Division of Cancer Prevention (DCP)
    National Cancer Institute (NCI)
    Telephone: 240-276-7126
    Fax: 240-276-7845
    Email: mazurchukrv@mail.nih.gov

    Page Limitations

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

    Instructions for Application Submission

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

    SF424(R&R) Cover

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

    SF424(R&R) Project/Performance Site Locations

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

    SF424(R&R) Other Project Information

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

    SF424(R&R) Senior/Key Person Profile

    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.

    Restricted Travel Expenses Budget: Applicants to this FOA are encouraged to budget for travel for the PD(s)/PI(s) to the Consortium for Imaging and Biomarkers Annual Investigator meetings.

    R&R Subaward Budget

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

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    Research Strategy:

    The Research Strategy should clearly describe the following within the appropriate section (i.e., Approach, Significance, Research Design, and Innovation).

    Information to be included in each grant application, but not limited to bulleted items, are listed below:

    Approach

    • The approach and methodology proposed will be unique to the unmet clinical need specifically addressed by each application. Whether or not the proposed approach is valid in the context of the grant application is based on many metrics, proposed research design, statistical power, etc. It is strongly encouraged that the proposed approach be succinctly described in detail and that it addresses possible weaknesses while clearly stating the strengths in terms of added value in screening, early detection, risk assessment and clinical management decisions.

    Significance

    Succinctly discuss how the proposed research improves diagnostic performance with regard to:

    (1) developing methodology for the early identification of lethal cancer versus non-lethal disease, (2) minimize/better manage overdiagnosis and (3) reduce false positives and false negatives.

    • Summarize how the proposed approach ultimately brings novel insight and understanding to cancer screening, early detection, active surveillance, characterization of high risk cohorts and cancer prevention.
    • Discuss how any proposed technological advances could ultimately be applied to improve screening, early detection, risk assessment and identify lethal cancers from non-lethal disease at the earliest time possible.

    Research Design

    • The potential difficulties and limitations of the proposed methodology and alternative approaches to achieve the aims should be identified and succinctly discussed.
    • Describe how the technological approach addresses an unmet clinically significant need.
    • Describe and define the target population(s) that will be used in the proposed research. Target population(s) may be derived from high risk cohorts including subjects participating in genetic screening, active surveillance, and familial risk screening or other differential diagnostic tests. PD/PI's need to succinctly describe and address well-defined clinically significant questions. Similarly, all animal model(s) as well as the target population(s) proposed in their research project for screening, early detection or risk assessment must be clearly described and defined within the context of the question being asked and how it addresses an unmet clinical need. Specifically, the unmet clinical need that is addressed in the research project must be clearly stated as well as how the proposed research could be applied in a clinical environment to overcome current weaknesses.

    It should be noted that screening, early detection and risk assessment are clinical management decision processes that are independent of technology (technology agnostic). The context of clinical management decisions and differential diagnosis are very important and are not just the result of a test, but are often derived from many metrics, complex physiologic interactions and multiple diagnostic evaluations longitudinally collected and evaluated over time.

    • PD/PI's should include a tentative sequence or timeline for the project as well as tangible milestones that will be met longitudinally during the course of the proposed research. The timeline and milestones aid reviewers and Program for assessing progress and accomplishments during the funding period.

    Innovation

    • Imaging, biomarkers, digital pathomics and other -omic data are rich sources of information regarding normal and disease processes including architecture, cell diversity, morphology and altered molecular pathways. However, the development of a more complete understanding of disease progression is needed.

    As an example, N-dimensional representations and advanced analytics have been hampered by the traditional two-dimensional (2D) visualization formats typical of diagnostic exams and histologic slides that often lack co-registration/cross-correlation to diagnostic images and biomarker(s) data. Therefore, the development of a scalable and searchable image-based approach for multi-platform analytics and visual discovery that integrates imaging, biomarkers, meta data, digital pathomics and other -omic data while allowing spatial, functional, and temporal analytics to be performed including, but not limited to, artificial intelligence and virtual reality visualization techniques would represent a significant innovative advance over current methods.

    • Principal Investigator(s) (PD/PI's) are asked to discuss and highlight the innovative aspects of their research design and to assemble a team of experts to address identified problems as well as to develop protocols, models and methods. The incorporation of advanced analytical methods to accelerate discovery and data visualization would be considered innovative and responsive. However, specific assessments of innovation are subjective by their inherent nature and will remain the responsibility of reviewers to evaluate.

    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, with the following modification:

    • All applications, regardless of the amount of direct costs requested for any one year, should propose a Data Sharing Plan.

    Appendix:

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

    PHS Human Subjects and Clinical Trials Information

    When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    Delayed Onset Study

    Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

    PHS Assignment Request Form

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

    Foreign Institutions

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

    3. Unique Entity Identifier and System for Award Management (SAM)

    See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

    4. Submission Dates and Times

    Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

    Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

    Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

    Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

    All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

    7. Other Submission Requirements and Information

    Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

    Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

    For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

    Important reminders:

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

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

    See more tips for avoiding common errors.

    Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

    Requests of $500,000 or more for direct costs in any year

    Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

    Only the review criteria described below will be considered in the review process.

    Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

    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.

    Overall Impact

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

    Scored Review Criteria

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

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

    Specific for this FOA: If the aims of the project are achieved, how will technological advances improve the integration of imaging, biomarkers, pathomics and other -omic data? Will the approach/methodology have an advantage over existing/alternate approaches? Does the research outcome have the potential to add new insights to the cancer research problem that is being addressed? Can the proposed approach/methodology, be further developed so as to address a significant unmet clinical need either now or in the future?

    In addition, for applications involving clinical trials:  Are the scientific rationale and need for a clinical trial to test the proposed hypothesis 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? 

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

    Specific for this FOA:  Do the project team members and/or associated collaborators have the multidisciplinary expertise required to successfully accomplish the specific aims proposed? For example, if appropriate and applicable, is sufficient expertise included from the fields of imaging, biomarkers, pathomic and other -omic methodology, preclinical models, clinical research, biomedical engineering, advanced analytical approaches, visualization of N-dimensional data, biomedical informatics, etc. to successfully complete the goals of the proposed research? Does at least one project team member have prior experience and/or necessary qualifications in cancer research to support the successful execution and implementation of the proposed project? Are there sufficient demonstrated interaction and collaboration between researchers to suggest successful completion of the proposed specific aims?

    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?

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    Specific for this FOA:   Do similar tools currently exist for early cancer detection? If so, how innovative and/or novel is the specific application of the proposed approach or technology in the context of cancer research?

    In addition, for applications involving clinical trials:  Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, specificity, potential for information or potential to advance scientific knowledge or clinical practice?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

    If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

    1) the protection of human subjects from research risks, and

    2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?  

    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, 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 in accrual addressed, if applicable, 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? 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 rigor, reproducibility, quantitation and quality control been addressed? Is there a plan to address data analytics and visualization schemes within the proposed period of the award?

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?   

    Specific for this FOA: Has the applicant established collaborations relevant for the project by engaging the fields of cancer imaging, biomarkers, pathomics and other -omic data as appropriate? Does the project take advantage of various co-registration and cross-correlation methodology, advanced analytics suitable for visualization of N-dimensional data sets as a function of spatial, functional and temporal dynamics? Do the letters of collaboration and institutional support show strong commitment to the project?

    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?   

    Additional Review Criteria

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

    Study Timeline

    Specific for 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.

    Additional Review Considerations

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

    Applications from Foreign Organizations

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

    Select Agent Research

    Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

    Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review (CSR), 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:

    • 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.
    • Will receive a written critique.

    Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

    • Scientific and technical merit of the proposed project as determined by scientific peer review.
    • Availability of funds.
    • Relevance of the proposed project to program priorities.
    3. Anticipated Announcement and Award Dates

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

    If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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

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

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

    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: Grantee 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 awardee 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).  

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, 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 law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

    Not Applicable

    3. Reporting

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

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

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

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

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

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

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

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

    Scientific/Research Contact(s)

    Sudhir Srivastava, Ph.D., MPH
    National Cancer Institute (NCI)
    Telephone: 240-276-7028
    Email:  srivasts@mail.nih.gov

    Richard Mazurchuk, Ph.D.
    National Cancer Institute (NCI)
    Telephone: 240-276-7126
    Email: mazurchukrv@mail.nih.gov

    Guillermo Marquez, Ph.D.
    National Cancer Institute (NCI)
    Telephone: 240-276-7035
    Email: marquezg@mail.nih.gov

    Peer Review Contact(s)

    Xiang-Ning Li, MD, Ph.D.
    Center for Scientific Review (CSR)
    Telephone: 301-435-1744
    Email: lixiang@csr.nih.gov

    Financial/Grants Management Contact(s)

    Amy R. Bartosch
    National Cancer Institute (NCI)
    Telephone: 240-276-6912
    Email: amy.bartosch@nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

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

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