Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	Revision Applications to R01 Awards for Research on Imaging and Biomarkers for Early Cancer Detection (R01)
Activity Code	R01 Research Project Grant
Announcement Type	New
Related Notices	June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. August 7, 2013 - See Companion PAR-13-318. Revision Applications to P50 Awards for Research on Imaging and Biomarkers for Early Cancer Detection (P50). August 7, 2013 - See Companion PAR-13-317. Revision Applications to P01 Awards for Research on Imaging and Biomarkers for Early Cancer Detection (P01). May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PAR-13-177
Companion Funding Opportunity	PAR-13-189, R01 Research Project Grant PAR-13-176, U01 Research Project - Cooperative Agreements Revisions PAR-13-175, P01 Program Project Grant Revisions PAR-13-174, P50 Specialized Centers Revisions
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.394
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) invites research project grant (R01) revision applications from investigators with active NIH R01 research project grant awards to support an expansion of the scope of funded R01 project grant awards through the addition of one or more new specific aims. Revision applications are expected to focus oncombined imaging and biomarker approaches to improve screening, early cancer detection and diagnosis by integrating multi modality imaging strategies and multiplexed biomarker methodologies.

Posted Date	April 11, 2013
Open Date (Earliest Submission Date)	June 10, 2013
Letter of Intent Due Date(s)	30 days before the due date.
Application Due Date(s)	July 10, 2013, December 11, 2013, July 10, 2014, December 11, 2014, July 10, 2015, December 11, 2015, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	July 10, 2013; December 11, 2013; July 10, 2014; December 11, 2014; July 10, 2015; December 11, 2015, by 5:00 PM local time of applicant organization.
Scientific Merit Review	October-November 2013, February-March 2014, October-November 2014, February-March 2015, October-November 2015, February-March 2016
Advisory Council Review	January 2014, May 2014, January 2015, May 2015, January 2016, May 2016
Earliest Start Date	April 2014, July 2014, April 2015, July 2015, April 2016, July 2016
Expiration Date	December 12, 2015
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the 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.

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

This Funding Opportunity Announcement (FOA) invites Revision research project grant (R01) applications from investigators with active NIH R01 research project grant awards to support an expansion of the scope of funded R01 research project awards through the addition of one or more new specific aims. Revision applications are expected to focus on combined imaging and biomarker approaches to improve screening and early cancer detection by integrating multimodality imaging strategies and multiplexed biomarker methodologies. The objective of this FOA is to stimulate and support cancer imaging and biomarker research to develop, optimize, and clinically validate novel methods to:

Detect cancers at the earliest stages possible;

• Reduce overdiagnosis;
• Reduce false positive tests; and
• Identify lethal cancers from non-lethal disease.

These goals can be met by a research strategy involving preclinical and clinical investigations to improve early cancer detection and diagnosis 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 direct clinical application is maintained. In these instances, an established reference standard or gold standard will be required for verification and validation of the proposed approach.

This FOA will utilize the NIH Research Project Grant (R01) mechanism and target revision applications from currently funded NIH R01 Research Projects with at least two (2) years of support remaining on the parent grant at the estimated time of award. Applicants responding to this FOA may take advantage of the option to designate multiple Program Director(s)/Principal Investigator(s) (PDs/PIs), each of whom would contribute unique expertise and scientific insights toward the successful completion of the proposed research.

The revision application must maintain the same Contact PD/PI listed on the parent grant. However, the grantee can request: (i) a change from a single PD/PI to a multiple PD/PI as part of this application, or, (ii) a change in the multiple PD/PI Leadership Plan if the funded parent R01 is a multiple PD/PI based grant. In either case, a new or modified multiple PD/PI Leadership Plan must be included.

Clinical Needs: 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 cancer 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 or 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 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 and biomarkers so as to provide added value to the parent award. In the context of this FOA, a biomarker is 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. Imaging is also included in this definition; however, for the purpose of this FOA, imaging refers to visual representation of cancer cells and cellular features and molecular analytes (genomic, proteomics, metabolomics, and other 'omics') for the purpose of medical diagnosis or data collection, using any of a variety of radiographic, sonographic, and other technologies to create a graphic depiction of the cancer cell and its surrounding in question. Both imaging and biomarkers can be derived from tissue, cancer cells, serum, plasma, urine, and/or other bodily fluids.

Two clinical examples are provided below to illustrate possible approaches appropriate 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 U.S. Food and Drug Administration (FDA) for use in a urine-based 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 pathologic, molecular, genetic, and imaging predictive markers as well as the evaluation of their validity and reliability is critical for advancing of our understanding the natural history of prostate cancer and for establishing guidelines to be used for 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 moderate grade cancer (Gleason grade 5-7). A decision regarding treatment or active surveillance needs to be made. In such cases, the application of a functional imaging test might be used to determine cancer extent and assess cancer aggressiveness.

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

Lung Cancer: Indeterminate lesion on imaging triggers subsequent biomarker(s) 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 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.

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

Scientific areas appropriate for Revision Applications under this FOA

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

• Use of molecular diagnostic tests to evaluate lesions observed by imaging to distinguish aggressive from indolent cancer or benign lesion from cancer.
• Use of imaging to evaluate biomarker results to improve sensitivity and specificity of early detection and diagnostic tests.
• Correlation of imaging with genomic results (radiogenomics) or other omics' results, such as the rich TCGA database.
• Combine and develop multiplexed panels of both multimodality molecular imaging and multiplexed biomarker panels that could improve current standards-of-care for screening, early cancer detection or diagnosis.

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 perform 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 histologic approaches; and/or
• 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 and clinical decision support for combining laboratory and imaging biomarkers.

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 appropriate 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, computed tomography (CT), ultrasound (US), photo acoustic imaging (PAI), nuclear polarization (NP) and photonic based approaches.

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

• Early Detection Research Network (EDRN);
• Alliance of Glycobiologists (AG);
• American College of Radiology Imaging Network (ACRIN);
• Network for Translational Research (NTR);
• Quantitative Imaging Network (QIN); and/or
• Related public resources such as:
  • The Cancer Genome Atlas (TCGA);
  • Cancer Imaging Archive (TCIA); and
  • EDRN data archives and biorepositories.

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.

Research projects that are not appropriate for this FOA

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

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	Resubmission (of revision applications submitted to this FOA). Revision R01 applications from active NIH R01 research project awards. The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
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	The amount of requested budget may not exceed $150,000 Direct Costs per year.
Award Project Period	Applicants may request support for up to two (2) years, not to exceed the remaining number of years on the parent grant. The parent grant must be active when the application is submitted. If a no-cost extension is needed on the parent grant, it must be in place before the revision application is submitted.

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

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)

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.

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) (formerly CCR) 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 mustobtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

The parent grant must be an active NIH R01 award. There must be at least two (2) years remaining on the parent grant at the estimated time of award. The revision application must maintain the same Contact PD/PI listed on the parent grant. However, the grantee can request a change in the Multiple PD/PI Leadership Plan as part of this application.

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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.
Cancer Biomarkers Research Group
Division of Cancer Prevention
National Cancer Institute
9609 Medical Center Drive, Room 3100
Rockville, MD 20850
Telephone: 240-276-7126
E-mail: [email protected]

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

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

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

The PD(s)/PI(s) on the revision must include the same PD(s)/PI(s) on the parent grant. Applicants responding to this FOA may take advantage of the option to designate multiple Program Director(s)/Principal Investigator(s) (PDs/PIs), each of whom would contribute unique expertise and scientific insights toward the successful completion of the proposed research.

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

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

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

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

A revision application may be submitted to request support for a significant expansion of a project’s scope or research protocol. Applications for revisions are not appropriate when the sole purpose is to restore awards to the full SRG-recommended level if they were administratively reduced by the funding agency. A revision application should not be submitted until after the original application has been awarded and must not extend beyond the term of the current award period.

Introduction to the Application: Describe the nature of the supplement and how it will influence the specific aims, research design, and methods of the current grant. The body of the application should contain sufficient information from the original grant application to allow evaluation of the proposed supplement in relation to the goals of the original application.

Specific Aims: Succinctly list the specific objectives and the goals of the proposed research. Summarize expected outcomes and milestones that will be achieved. Specific Aim(s) must be distinct for the Revision application and specifically address the objective(s) of this FOA.

Research Strategy: Describe the proposed research including methodology, possible outcomes, relevance, and how expected results might be applied in a clinical setting. Include sufficient detail to allow assessment of the proposed additional Specific Aim(s) in the context of the priorities defined in this FOA.

The objective of this FOA is to stimulate and support collaborative cancer imaging and biomarker research to develop, optimize, and clinically validate novel methods to:

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

Describe how the Revision application addresses unmet clinical needs and will provide added value to the scope of the parent R01 award.

Multiple PD/PI Leadership Plan: If adding PDs/PIs to a single PD/PI parent grant, or, if any other change to the leadership team of an existing multiple PD/PI parent grant is planned, a Multiple PD/PI Leadership Plan must be included to reflect these changes.

Letters of Support: Attach all appropriate letters of support or collaborations, including any letters necessary to demonstrate the support of collaborators such as senior/key personnel and Other Significant Contributors included in the grant application. Letters are not required for personnel (such as research assistants) not contributing in a substantive, measurable way to the scientific development or execution of the project. For consultants, letters should include rate/charge for services.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Significance

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

Specific to this FOA: If the aims of the project are achieved, how will the combined imaging and biomarker approach increase our understanding and help to overcome current clinical challenges associated with screening and early cancer detection?

Investigator(s)

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

Specific to this FOA: Do the investigators have complementary experience in imaging and biomarkers as applied to the cancer problem?

Innovation

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

Specific to this FOA: Does the research scope address innovative methods in imaging or biomarker(s)? NOTE: In the context of this FOA it should be emphasized that applications including an established imaging method with an investigational biomarker, or an established biomarker with an investigational imaging approach would necessarily be considered innovative.

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

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: Do the PDs/PIs and assembled collaborative research team have access to the appropriate resources, such as specimen banks of clinically annotated samples of normal and cancer cases, and mode(s) of detection to successfully complete the proposed aims of the project, e.g., are screen-detected and interval-detected cancers included for lung cancer projects?

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

Not Applicable

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.

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

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

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.

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

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the 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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Phone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

For issues related mainly to early cancer detection and biomarkers, please contact:

Richard Mazurchuk, Ph.D.
Cancer Biomarkers Research Group
Division of Cancer Prevention
National Cancer Institute
Telephone: 240-276-7126
E-mail: [email protected]

For issues related mainly to imaging, please contact:

Keyvan Farahani, Ph.D.
Cancer Imaging Program
Division of Cancer Treatment and Diagnosis (DCTD)
National Cancer Institute
Telephone: 240-276-5921
E-mail: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Samantha Farrell, M.H.S.
Grants Management Specialist
Office of Grants Administration
National Cancer Institute
Telephone: 240-276-6295
E-mail: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.