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

The overall objective of this Funding Opportunity Announcement (FOA) is to support translational/epidemiological projects to study adducts to cellular macromolecules as indicators of exposures to cancer risk factors in human populations. The priority is on projects that will focus on adductomic approaches, i.e., address some aspects of the totality of adducts. The goals should be centered on linking adductomic-based indicators of exposures to exogenous and endogenous cancer risk factors identification for prevention.

All projects proposed in response to this FOA are expected to be based on comprehensive use of human biospecimens for which detailed medical data are available (e.g., biospecimens from the NCI-supported cohort studies). The research may focus on such aspects as: 1) identification and evaluation of adducts as indicators of cancer risk using samples from existing cohort studies, cancer prevention trials, and populations that may be exposed to certain environmental factors and 2) application of adductomic approaches in identifying subgroups of subjects (stratification) with varied risk of cancer, and 3) combination of specific adductomic aspects with other molecular signatures for cancer risk assessment.

In addition, projects that evaluate the potential roles of adducts in cancer etiology and use adducts for gene-environment interaction research (GxE) may also be appropriate provided that such projects are based on appropriate sets of human biospecimens (such as specimens from cohorts studies supported by NIH).

This FOA uses the Cooperative Agreement funding mechanism (U01) and is intended for well-developed clinically relevant, translational/epidemiological projects. Whereas each of these projects is expected to be conducted independently, the NCI will coordinate across the awardees various common aspects, including the distribution and usage of specimens from the NCI-supported cohort studies.

Applicants considering projects focused on adducts/adductomics in the context of cancer, but oriented more on basic discovery/exploration of the potential utility of adductomic approaches rather than their clinical translation, should consider two companion FOAs of similar scientific scope listed below:

• PAR-15-308 for well-developed projects focusing on basic research on adducts/adductomic approaches (using R01 funding mechanism); and
• PAR-15-309 for exploratory pilot projects of the same scope (using R21 funding mechanism).

Key Definitions. For the purpose of this FOA, the terms adductomics and adductomic approaches , refer to various studies aimed at exploring at least some aspects of the totality of adducts in the cell, tissues, and/or organisms. For example, adductomic studies may aim to identify the patterns of DNA adducts along the sequence of genomic DNA, to characterize diverse types of DNA adducts and quantify their total levels, and/or to characterize the total levels of adducts formed by all exogenous and endogenous reactive electrophiles with a specific nucleophilic target, such as a specific protein(s) in serum and/or in a range of tissues.

Note:

Projects that focus on adductomic technology/methods development are generally not expected to be supported by the NCI.

Various reactive compounds that are often carcinogenic form either directly or through their metabolically active intermediates covalent conjugates with cellular macromolecules (primarily DNA, RNA, and proteins). These conjugates are collectively referred to as adducts . The carcinogen-induced DNA-, RNA-, and protein adducts contribute to tumor emergence and are highly relevant markers of exposures to cancer risks.

Among all types of adducts associated with elevated cancer risks, DNA adducts have been most widely studied with regard to their roles in cancer initiation. DNA adducts, if not correctly repaired in cells, can exert adverse biological effects contributing to mutagenesis, cancer initiation, and progression. Particularly important in this context can be unrepaired DNA adducts (and the resulting mutations) in oncogenes and tumor suppressor genes. Protein and other types of adducts have also been studied to investigate cancer etiology, exposures to carcinogenic factors, and risks of cancer development. It is clear that adducts in specific genomic regions and/or to specific proteins can play important roles in pathways involved in cancer initiation and development. However, systematic studies of relevant adduct patterns have been hampered by technical challenges of assessing and quantifying more than few selected types of adducts in a broader range of targets, including the distribution of such adducts across the genome and/or proteome.

Recent advances make it possible to characterize adducts at increasingly complex and global scales, including, for example, comprehensive detection and quantification of various types of adducts, genome-wide profiling of DNA adducts, or the detection of protein adducts across the proteome. These advances gave rise to a new scientific field of adductomics, with the ultimate goal to understand, identify, and/or measure all types of adducts and their distribution patterns with all cellular targets. Adductomics could provide opportunities for systematic discovering and characterizations of various types of adducts. Such studies have a high potential for identifying specific adduct profiles as molecular signatures relevant to gene-environment interactions (G E) impacting cancer initiation as well as providing a source of cancer risk biomarkers.

Further efforts are warranted to take full advantage of the potential of adductomics for advances in cancer risk identification and cancer prevention. For example, integrative research is needed to connect the pattern of adducts, DNA repair capacity, and environmental exposures for cancer risk identification. Furthermore, there are needs to conduct correlative studies to associate not only specific adduct types but also the adductomic patterns as molecular signatures reflective of environmental and lifestyle factors in populations at diverse risks for cancer (including the identification of those sub-populations at particularly elevated risks).

Using adductomic findings as indicators of exposures to cancer risk may have important translational aspects in risk assessments. Such exposure indicators may also have a role in strategies for cancer prevention. It is expected that the translational exploration of the adductomic data and approaches to develop and validate the molecular signatures for risk identification and cancer preventions will be greatly facilitated by using specimens from existing cohorts with proper clinical and exposure data. Translational research on applying adductomic approach to assess cancer risk will benefit prevention.

This FOA encourages translational/epidemiological research on the evaluation and validation of the adductomic strategies/tools to detect/characterize quantify, as appropriate, multiple types of adducts and/or patterns of adducts across targeted macromolecule(s), different types of cells, tissues, etc. as indicators of exposures to cancer risk factors and/or tools aiding the optimization of cancer prevention strategies. The projects should be based on the comprehensive use of human tissues/specimens with appropriate medical information. Other types of human specimens or other models may be used only in auxiliary role. The projects are expected to generate new ways for the assessment of exposures to cancer risk factors and/or for facilitating the optimization of cancer prevention strategies in human populations. The proposed projects should be based on strong preliminary data reflecting basic research and/or early determinations in the human populations.

Applicants are encouraged to consider the following areas for the projects proposed in response to the FOA:

• Connections between various adductomic aspects and environmental exposures that may correspond to elevated cancer risks at the population levels and characterization of unrepaired adducts or a slower adduct removal in some individuals that may indicate higher risk of mutation and carcinogenesis
• Epidemiological characterizations of broad adduct types either selected in a rational way, for examples, corresponding to adducts caused by the most relevant environmental factors and/or monitored in an unbiased way attempting to detect all and any adducts that might be in the targeted macromolecules, tissues, organs, and body fluid.
• Evaluation of the utility of specific adduct patterns as predictive molecular signatures that may be useful for "precision" cancer prevention. Such patterns may include, for example, quantification of a range of adduct types, distribution of DNA adducts in several key genomic locations (like tumor suppressor genes or oncogenes), or other characteristics of multiple adducts implicated by the preliminary data to be relevant.

Examples of relevant research directions include but are not limited to:

• Evaluate and validate adductomics for cancer risk stratification using cohorts with well characterized exposure information and demography;
• Utilize adductomic approach in specimens such as blood, plasma, sera, urine, saliva to generate adduct profiles that distinguish cases from controls to identify patterns that indicate elevated cancer risk;
• Evaluate adductomic signatures in populations exposed to diverse environmental factors including chemicals, dietary mutagens, mycotoxins, pesticides, and other xenobiotcs with carcinogenic properties for identification of elevated cancer risks, and risk stratification and identification;
• Develop approaches to evaluate adducts in combination with other types of molecular signatures and images to increase sensitivity and specificity for risk identification;
• Evaluate DNA adducts that may promote specific driver gene mutations and perform studies applying integrated adductomic approaches to stratify cancer risk in populations;
• Validate studies comparing adduct levels in body fluids and relevant accessible tissues;
• Use adductomic approaches to study the risk of untested (or insufficiently tested) products, e.g., electronic cigarettes (e-cigarettes) in populations;
• Integrate bioinformatic approaches to identify adductomic profiles, sequences or patterns in target tissues for cancer risk assessment and GxE research
• Develop tissue and/or body fluid-based molecular dosimetry using adducts to measure chronic exposure to diverse environmental carcinogenic agents to aid cancer risk determinations in at-risk populations;
• Apply an adductomics approach(-es) to precision prevention strategies that would allow for customizing interventions based on different levels of individual risks;
• Conduct adductomic studies (focused on DNA and/or protein adducts) in high risk populations for assessing cancer risk and/or assessing the efficacy of cancer prevention strategies;
• Refine and apply novel technology, tools, methods, and/or algorithms suitable for population studies, e.g., to improve adduct identification, the sensitivity and reproducibility of adduct detection and quantification, and/or enhance ways to analyze population-derived adductomic data
• Apply adductomic approach for carcinogen exposure research.

U01 awardees will be expected to participate in an Adductomic Research Working Group that will provide a forum for exchange of information and sharing experiences among the investigators participating in the adductomic research. In addition to U01 awardees, the awardees of the companion R01 and R21 FOAs will also be encouraged to participate in this Working Group).

The programs listed below are examples of other NCI- -supported initiatives that may be useful for potential applicants as valuable resources (e.g., for developing collaborations, accessing accumulated available data and/or specimens etc.)

• Early Detection Research Network (EDRN), http://edrn.nci.nih.gov
• The Cancer Genome Atlas (TCGA), http://cancergenome.nih.gov/
• NCI Cohort Consortium, http://epi.grants.cancer.gov/Consortia/cohort.html
• Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, http://prevention.cancer.gov/plco
• National Lung Screening Trial (NLST), http://www.cancer.gov/clinicaltrials/noteworthy-trials/nlst.

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
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

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.

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

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

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, including Supplemental Grant Application Instructions 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:

Wendy Wang, Ph.D. M.Sc.
Division of Cancer Prevention (DCP)
National Cancer Institute (NCI)
9609 Medical Center Dr Rm 5E566- MSC
Bethesda, MD 20892-7362 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery

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

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

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.

All instructions in the SF424 (R&R) Application Guide must be followed. The following additional guidance applies.

Applicants should budget appropriate travel funds for the participation of one or two of PIs/PDs (or one PD/PI and another senior investigator) in person meetings of the Adductomic Research Working Group or, alternatively, meetings of all PDs/PIs of the Adductomic Research initiative (for all U01, R01, and R21 awards). These meetings will be held at least each other year at locations selected by the NCI, possibly NCI campus.

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:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address 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.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report 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.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. 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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Applicants are required to follow our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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.

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?

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

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?

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 human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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.

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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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.

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.

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.

Not Applicable

Not Applicable

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.

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.

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).

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

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 submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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 (DHHS) 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:

• Defining the scientific objectives and approaches, including research design and study protocol development, if applicable
• Overseeing study conduct, including data collection and analysis, quality control, and results publication;
• Accountability to the applicant organization officials and to the NCI for the performance and the proper conduct of the research supported by the U01 award in accordance with the terms and conditions that are stated in this FOA;
• Participating as a full member of the Adductomic Research Working Group;
• Participation in a Planning Meeting and one in person Working Group or PD/PI meeting in the first year, one Working Group or PD/PI meeting in each of the subsequent years of the award;
• Accepting and implementing the goals, priorities, procedures, and policies agreed upon by the Working Group to the extent consistent with applicable grant regulations;
• Cooperating with other PD(s)/PI(s) and the NIH staff members, as appropriate for the goals of the program;
• Overseeing the implementation of the approved data sharing plan; and
• Ensuring that experimental data and their format, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this FOA are compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Biomedical Informatics and Information Technology (CBIIT; http://cbiit.nci.nih.gov/).

In addition to these responsibilities and obligations, the PD(s)/PI(s) and their awardee institutions will be accountable for implementing the approved research resource sharing plan.

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

An NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement. Additional NCI staff members may be designated to have substantial involvement (e.g., in the role of Project Scientist or Project Coordinator).

The main responsibilities of substantially involved NCI staff members include, but are not limited to, the following activities:

• Coordinating the research activities among and for all the awardees and organizing the exchange of scientific information across the program, including coordination across the awardees of the distribution and usage of specimens from the NCI-supported cohort studies;
• Facilitating the interactions among participating researchers;
• Serving on the Adductomic Research Working Group;
• Serving as an information resource for the awardees about adduct research activities;
• Serving as a liaison and promoting interactions with other NIH-sponsored programs as appropriate (e.g., to facilitate collaborations);
• Advising the awardees on the matters related to the technical performance of the projects; and
• Monitoring the progress and performance of the awardees; and

Additionally, an NCI program director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Some Program Officials may also have substantial programmatic involvement (as Project Scientists/Coordinators).

The NCI reserves the right to withhold or reduce support for projects that fail to achieve their goals or awardees, who fail to comply with the Terms and Conditions.

Areas of Joint Responsibility include:

Investigators and NCI Program staff members will jointly establish the Adductomic Research Working Group, which will be composed, at a minimum, of the following members:

• Two representative [two PD(s)/PI(s) or a PD/PI and another senior investigator] from each U01 award, will be required to participate in the Working Group; and
• One or more of the NCI program staff members (e.g., a Project Scientist) will be a member of the Working Group. Other NCI staff members may participate in the Working Group activities as needed.

The Chair of the Working Group (who should be a PD/PI of an U01 award) will be selected by the Working Group.

The anticipated activities of the Adductomic Research Working Group include, but are not limited to, the following:

• Providing a forum for exchanging technical information that may be relevant and helpful to other awardees;
• Sharing information on the progress of individual projects;
• Identifying areas that may benefit from the standardization across the awardees and developing, as appropriate, standard operating procedure, protocols, and/or other relevant information;
• Working towards establishing standards and/or milestones applicable for further translational and clinical studies based on adductomic approaches;

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 DHHS regulation 45 CFR Part 16.

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: support@grants.gov

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

For inquires related to cancer prevention contact:

Wendy Wang, Ph.D. M.Sc.
National Cancer Institute (NCI)
Telephone: 240-276-7117
Email: wangw@mail.nih.gov

For inquires related to population studies contact:

Gabriel Lai, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7201
Email: laigy@mail.nih.gov

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Brian Iglesias
National Cancer Institute (NCI)
Telephone: 240-276-6278
Email: iglesiab@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 Part 75.