Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	Utilizing the PLCO Biospecimens Resource to Bridge Gaps in Cancer Etiology and Early Detection Research (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	New
Related Notices	July 14, 2015 - This PA has been reissued as PAR-15-297. June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. 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-13-036
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.393
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA), issued by the National Cancer Institute (NCI), encourages the submission of grant applications that propose to advance research in cancer etiology and early detection biomarkers, utilizing the advantages of the unique biorepository resources of the NCI-sponsored Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. The PLCO Biorepository offers high-quality, prospectively collected, serial pre-diagnostic blood samples from the PLCO-screened arm participants, and a onetime collection of buccal cells from the control arm participants. Available data associated with the biospecimens includes demographic, diet, lifestyle, smoking, screening results, and clinical data. This FOA supports a wide range of cancer research including, but not limited to, biochemical and genetic analyses of cancer risk, as well as discovery and validation of early detection biomarkers. The proposed research project must involve use of PLCO biospecimens; additionally, it should also take advantage of the unique characteristics of the PLCO biospecimens. Research projects that do not involve the use of PLCO biospecimens will not be supported under this FOA.

Posted Date	December 6, 2012
Open Date (Earliest Submission Date)	January 20, 2013
Letter of Intent Due Date(s)	30 days before the application due date
Application Due Date(s)	February 20, 2013; June 20, 2013; February 20, 2014; June 20, 2014; February 20, 2015; June 19, 2015, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	July 2013; November 2013; July 2014; November 2014; July 2015; November 2015
Advisory Council Review	October 2013; January 2014; October 2014; January 2015; October 2015; January 2016
Earliest Start Date	December 2013; April 2014; December 2014; April 2015; December 2015; April 2016
Expiration Date	June 20, 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), issued by the National Cancer Institute (NCI), encourages the submission of grant applications that propose to advance research in cancer etiology and early detection biomarkers, utilizing the advantages of the unique biorepository resources of the NCI-sponsored Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. The PLCO Biorepository offers high-quality, prospectively collected, serial pre-diagnostic blood samples from participants in the PLCO-screened arm, and a one-time collection of buccal cells from participants in the control arm. Tissue microarrays of formalin-fixed, paraffin-embedded (FFPE) tumor tissues are also available for a subset of the cases for selected cancers. This FOA supports a wide range of research including biochemical and genetic analyses of cancer risk, as well as discovery and validation of early detection biomarkers. The proposed research project must involve use of PLCO biospecimens; additionally, it should also take advantage of the unique characteristics of the PLCO biospecimens. Research projects that do not involve the use of PLCO biospecimens will not be supported under this FOA.

The PLCO, which was a randomized controlled cancer screening trial involving 155,000 participants from across the United States, was conducted to evaluate the effectiveness in reducing cancer-specific mortality of four screening programs: digital rectal examination and prostate specific antigen for prostate cancer; chest X-ray for lung cancer; flexible sigmoidoscopy for colorectal cancer; and the tumor marker CA125 in combination with transvaginal ultrasound for ovarian cancer. The main phase of the trial concluded in May 2012, and mortality outcomes have been published. PLCO participants are still being followed using a streamlined centralized approach in order to collect valuable data on cancer in the aging population. Information on trial design, screening protocols, publications, available types and numbers of biospecimens and associated data can be found on the PLCO website at http://www.plcostars.com.

The PLCO Biorepository offers high quality, pre-diagnostic, serial blood samples (serum/plasma/DNA/red cells/cryo-preserved whole blood) ideal for investigation of the causes and the natural history of various cancers, and for pivotal validation of promising blood-based early detection biomarkers. The PLCO Biorepository has supported a wide range of research in cancer etiology and early detection. To date, 118 research projects using the PLCO biospecimens have been initiated, resulting in over 150 research publications. More information about on-going research projects and publications can be found on the PLCO website at www.plcostars.com.

The purpose of this FOA is to stimulate areas of cancer research that require prospectively collected pre-diagnostic blood specimens available from the PLCO Biorepository. The proposed research project should not only involve use of PLCO biospecimens and data, but take advantage of their unique characteristics, in large part by focusing on research questions that cannot be adequately addressed by using clinical samples (samples collected following a diagnosis). In some cases, it may be necessary to include specimens from other sources in order to carry out the proposed research. In that case, the investigator should obtain approval from the other source to access the specimens and provide evidence of the approval.

Research projects that do not involve the use of PLCO biospecimens will not be supported under this FOA.

Some characteristics of the PLCO specimens and data include:

• Pre-diagnostic serum/plasma/lymphocyte DNA samples collected months to years before cancer diagnosis;
• Serial blood samples (which may include serum, plasma, and/or lymphocyte DNA) collected over a period of time up to 6 years;
• Detailed demographic, dietary, lifestyle, and clinical data (all cancer incidence and all cause mortality);
• Average-risk population;
• Tissue microarrays of FFPE tumor samples available for a subset of cases for breast, prostate, colorectal, lung, and ovarian cancers, with matching blood or DNA samples from the same person; and
• Genotype data from Genome Wide Association Studies (GWAS) available on a subset of prostate, lung, bladder, pancreatic, and kidney cancers.

Detailed information about the PLCO Biorepository, including sample availability, can be found on the PLCO website at www.plcostars.com. Given that any research project proposed in response to this FOA will be based on the use of PLCO specimens, interested investigators and applicants should first identify appropriate biospecimens and data by submitting a Preliminary Application Form on the PLCO website at www.plcostars.com. Instructions on how to submit the Preliminary Application Form will be provided on the same website. The PLCO staff will check if the needed biospecimens and data are available and the research can be done using the PLCO biospecimens. The applicant will be provided with a letter confirming the availability of the biospecimens and data within a short period of time. The applicant must include this letter in the grant application. If biospecimens from other resources are to be used, the investigator should provide a letter of approval from the other resource for accessing the required specimens.

Specific research areas of interest include, but are not limited to, the following:

• Identifying biomarkers of various environmental, biochemical, and genetic risk factors of cancer;
• Pivotal validation of early detection blood biomarkers in pre-diagnostic samples;
• Developing early detection and/or risk prediction models based on longitudinal patterns of the biomarkers;
• Identifying blood biomarkers that correlate with clinical behavior of the tumors, especially those that differentiate between aggressive and indolent cancers;
• Correlating blood biomarkers to tissue biomarkers, histological and molecular subtypes, and clinical behaviors; and
• Biomarker discovery in pre-diagnostic samples using high through-put, proven technologies.

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 Resubmission Revision 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	Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period	Scope of the proposed project should determine the project period. The maximum period is 5 years.

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 must complete the following registrations as described in the SF424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• Grants.gov
• eRA Commons

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 6 weeks prior to the application due date.

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.

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 NCI 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 research;
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s);
• Names of other key personnel;
• Participating institution(s); and
• Number and title of this funding opportunity.

The letter of intent should be sent to:

• Claire Zhu, Ph.D.
  Early Detection Research Group
  Division of Cancer Prevention
  National Cancer Institute
  9609 Medical Center Drive, Room 5E106
  Rockville, MD 20850
  Telephone: 240-276-7013
  Email: zhucla@mail.nih.gov

The forms package associated with this FOA includes all applicable components, mandatory 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 page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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

Research Strategy

The Research Strategy section of the application must include additional information relevant to the use of PLCO biospecimens. This additional information should address:

• Justification for why PLCO pre-diagnostic samples are required;
• When applicable, preliminary data demonstrating assay reproducibility and acceptable coefficients of variability;
• Specify and justify the time interval between diagnosis and collection of the requested samples (for example, within 3 years of diagnosis);
• Justification for sample volume and total number of samples;
• If requesting serial samples, provide information on the biomarker performance in other pre-diagnostic samples; and
• If proposing biomarker discovery, provide information on prior discovery efforts in clinical samples.

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, with the following modification:

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

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. In addition, the Appendix should contain the following letter(s).

• A letter to the applicant from the PLCO is required confirming the availability of the PLCO biospecimens and data that will be the basis for the research project proposed in the application; if specimens from other resources are to be used in conjunction with the PLCO specimens, a letter of approval from that resource for accessing the specimens is also required. For more information, see Part 2, Section I. above, go to the PLCO web site at www.plcostars.com, and contact the scientific/research contact persons indicated in Part 2. Section VII.

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 deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application before the deadline 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.

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 (SAM). 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 requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff 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.

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?

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?

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?

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?

In addition, aspects of Approach that are specific to this FOA include:

• Can the study aims be accomplished using PLCO specimens and data?
• Is justification provided for why pre-diagnostic specimens are needed?
• Is the time interval from diagnosis to collection of the requested samples specified and justified?
• Does the proposed research take advantage of the characteristics of the PLCO cohort?
• Is the proposed research duplicative or complementary to on-going PLCO research?
• Is the sampling plan consistent with the aims of the study?
• Are the sample volume and total number of samples justified? If applicable, does the assay technology allow use of minimal sample volume?
• If the proposed research requires serial samples, has (have) the marker(s) been tested in any pre-diagnostic samples? If so, were the results promising enough to warrant further testing in serial samples? Overall, is there convincing evidence that use of serial samples will provide substantial added value over what could be achieved using single time-point samples?
• If the proposed research is biomarker discovery, does the research use proven, mature technologies? Is a rationale given for why discovery in pre-clinical samples is needed for the particular cancer (for example, did prior discovery in clinical samples lead to failed validation in pre-clinical samples)?

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?

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 NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• 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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The PD(s)/PI(s) for each U01 award will have the primary authority and responsibility for the project as a whole, including defining the research objectives, conducting specific studies, analysis and interpretation of research data, and preparation of publications.

Specific rights and responsibilities will include the following:

• To ensure the validity of the research, PLCO specimens will be coded when released to the investigators and will remain blinded. The PD(s)/PI(s) will be required to submit to NCI all laboratory-generated data on all PLCO specimens, after which the samples will be unblinded. One year after the unblinding of the PLCO specimens, these data will be made available through the PLCO website to the scientific community.
• Representatives of each U01 award will be expected to work with the NCI Project Scientist (whose responsibilities are defined below) on the coordination of research program activities. These actions may involve (but will not be limited to) the participation in the appropriate meetings and/or working groups, and/or teleconferences as needed;
• In addition to providing standard annual progress reports, each U01 awardee will be responsible for providing other relevant information to the NCI Project Scientist, and to coordinate and cooperate with NCI staff and other members of the Program.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff members have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

A designated NCI Program Director acting as a Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The NCI Project Scientist will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications.

Specifically, the NCI Project Scientists will:

• Work with the U01 awardees to ensure that appropriate samples are selected for the study. When applicable, a common sampling plan may be developed for similar studies (e.g., biomarker validation studies for a particular cancer).
• Coordinate and facilitate the interactions among the U01 awardees under this initiative;
• Serve as liaison between the research awardees and NCI staff members and investigators involved in the program, facilitating interactions and scientific integration between the U01 awardees;
• Promote and help coordinate collaborative research efforts that involve interactions with other NCI-sponsored programs, projects, and centers;
• Participate in program meetings;
• Review all major transitional changes that the awardees might propose (e.g., a change in partnering institution) and advice on their appropriateness prior to implementation to assure consistency with the goals of this FOA;
• Provide technical assistance and advice to the awardees as appropriate;
• Assist in the interaction between the U01 awardees and investigators at other institutions, as appropriate for the program;
• Assist in avoiding unwarranted duplication of effort with other NIH efforts;
• Monitor institutional commitments and resources to the awardees;
• Suggest modifications to research efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- specifically, the NCI Project Scientist may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures;
• Develop working groups and trans-project efforts as needed;
• Organize and conduct regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the awardees; and
• Additionally, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice. A Program Official may also have substantial programmatic involvement (as a Project Scientist) and may be the same person as Project Scientist. In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications, or will seek NCI waiver according to the NCI Procedures for Management of Conflicts of Interest.

Areas of Joint Responsibility include:

The NCI Project Scientist and the PD(s)/PI(s) of the U01 awards funded under this research Initiative will be jointly responsible for the coordination of intra-program activities and the scientific integration of individual projects.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting; one NIH designee; and a third designee with expertise in the relevant area who is chosen by the other two. In the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

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.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Claire Zhu, Ph.D.
Early Detection Research Group
Division of Cancer Prevention
National Cancer Institute
9609 Medical Center Drive
Room 5E106
Rockville, MD 20850
Telephone: 240-276-7013
Email: zhucla@mail.nih.gov

Jo Ann Rinaudo, Ph.D.
Cancer Biomarkers Research Group
Division of Cancer Prevention
National Cancer Institute
9609 Medical Center Drive
Room 5E612
Rockville, MD 20850
Telephone: 240-276-7133
Email: rinaudoj@mail.nih.gov

Referral Officer
Division of Extramural Activities
National Cancer Institute
Tel: (240) 276-6390
Fax: (240) 276-7682
E-mail: ncirefof@dea.nci.nih.gov

Cammie La
Office of Grants Administration
National Cancer Institute
Telephone: 240-276-6323
Email: lac@mail.nih.gov

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.