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

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

National Institute of Environmental Health Sciences (NIEHS)

Funding Opportunity Title

Innovative Basic Research on Adducts in Cancer Risk Identification and Prevention (R21)

Activity Code

R21 Exploratory/Developmental Research Grant

Announcement Type

New

Related Notices
  • NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015)
  • NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals (November 18, 2015)
  • NOT-OD-16-011 - Implementing Rigor and Transparency in NIH & AHRQ Research Grant Applications (November 18, 2015)
  • August 21, 2015 - Correction of Due Dates for Letters of Intent for PAR-15-309. See Notice NOT-CA-15-031.
Funding Opportunity Announcement (FOA) Number

PAR-15-309

Companion Funding Opportunity

PAR-15-308 R01 Research Project Grant

PAR-15-307 U01 Research Project – Cooperative Agreements

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

93.393, 93.394,; 93.242, 93.395, 93.113   

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA), encourages research projects focused on adducts to cellular macromolecules as indicators of exposures to cancer risk factors relevant to human populations. The priority is on projects that will focus on adductomic approaches, i.e., address some aspects of the totality of adducts. These projects should explore the basic aspects of adducts/adductomics that may have a potential utility in cancer detection, cancer prevention, and/or assessing cancer risks. The projects should be relevant to adducts in humans and human populations but may be conducted using various model systems (e.g., cultured cells, animals, etc.). The use of human biospecimens is encouraged and expected if appropriate but not required.

In well-justified cases, innovative studies using the adductomic approaches in the context of cancer etiology and/or gene-environment interaction research may also be appropriate. For projects intended for NIEHS support, the focus may be on innovative technology and method development.  

Key Dates
Posted Date

July 24, 2015

Open Date (Earliest Submission Date)

October 23, 2015

Letter of Intent Due Date(s)

30 days prior to Application Due Date

Application Due Date(s)

November 23, 2015; July 11, 2016, November 22, 2016; July 11, 2017, November 21, 2017; July 11, 2018, by 5:00 PM local time of applicant organization. All types of applications allowed for this funding opportunity announcement are due on these dates.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February-March 2016; October-November 2016; February-March 2017; October-November 2017; February-March 2018; October-November 2018  

Advisory Council Review

May 2016; January 2017; May 2017; January 2018, May 2018; January 2019

Earliest Start Date

July 2016; April 2017; July 2017; April 2018; July 2018; April 2019

Expiration Date

July 12, 2018

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.


There are several options to submit your application to the agency through Grants.gov. You can use the ASSIST system to prepare, submit and track your application online. You can download an application package from Grants.gov, complete the forms offline, submit the completed forms to Grants.gov and track your application in eRA Commons. Or, you can use other institutional system-to-system solutions to prepare and submit your application to Grants.gov and track your application in eRA Commons. Learn more.

Problems accessing or using ASSIST should be directed to the eRA Service Desk.
Problems downloading forms should be directed to Grants.gov Customer Support.
Table of Contents

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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Purpose

The overall objective of this Funding Opportunity Announcement (FOA) is to support innovative research on adducts to cellular macromolecules as indicators of exposures to endogenous and exogenous cancer risk factors relevant to exposures 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 ultimate goal is to discover and characterize the utility of adductomic-based exposure indicators for cancer detection, cancer prevention, and/or assessing cancer risks.

These projects should explore the basic aspects of adducts/adductomics that may have a potential utility in cancer detection, cancer prevention, and/or assessing cancer risks. The projects should be relevant to adducts in humans and human populations but may be conducted using various model systems (e.g., cultured cells, animals, etc.). The use of human biospecimens is encouraged if appropriate but not required.

In addition, projects that evaluate the potential roles of adducts in cancer etiology and conduct studies of adducts for gene-environment interaction research (GxE) may also be appropriate.

For projects intended for NIEHS support, the focus may be on innovative technology and method development.

This FOA is intended for exploratory pilot projects with limited preliminary data. For well-developed projects based on strong preliminary data with similar scientific scope, prospective applicants are advised to consider the R01 companion FOA (PAR-15-308).  Both FOAs will support basic, discovery-oriented research.

For clinically-relevant translational and/or epidemiological projects exploring adducts/adductomic approaches and markers in human populations (with a comprehensive use of human biospecimens for which detailed medical data are available) potential applicants should consider a third companion FOA  (PAR-15-307) that uses the U01 funding mechanism.

Key Definitions. For the purpose of this FOA, the terms “adductomics” and “adductome/adductomic approaches”,  refer to various studies aimed at exploring at least some aspects of the totality of adducts in the cell, tissues, and/or organism. 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.

 
Background

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 endogenous and exogenous 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).

Exploratory novel basic research is needed to investigate the biological basis on the formation of adducts and their resistance to repair as well as to increase the knowledge of adducts in pathways in carcinogenesis for cancer risk identification.

Specific Research Objectives

This FOA encourages basic research focused on using the adductomic approaches to discover, characterize, and/or quantify, as appropriate, multiple types of adducts and/or patterns of adducts  across targeted macromolecule(s), different types of cells, tissues, etc. The projects may use diverse model systems, with the use of human tissues/specimens encouraged as appropriate but not required. However, the project design and outcomes should be highly relevant to humans and human populations in terms of potential novel approaches to the assessment of exposures to cancer risk factors and/or potential utility in optimizing cancer prevention strategies.

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

  • Basic adductomic characterization/cataloging of broad ranges of adduct types differing in their origin, types, location (target), etc. types. Such characterizations may serve the goal of increasing the understanding of adducts caused by the specific environmental factors of high relevance to human cancers. Alternatively, adducts patterns may be monitored in an unbiased way attempting to detect all and any adducts that might be formed in the targeted macromolecules, tissues, and organs;
  • Determination of DNA adducts genome-wide or at least in many sites, including specific known important genomic regions, for example, in tumor suppressor genes or oncogenes.  Such determinations should cover a range of adduct types and should be connected to the main theme of comprehensive characterizations of DNA adducts;
  • Connections/relationships between changes/patterns of adducts detectable using adductomic approaches and environmental exposures that may modify (elevate) cancer risk;
  • Adductomic-based characteristics/patterns (e.g., adductomic molecular signatures, genomic distribution of adducts, etc.) that may serve as markers linking exposures to cancer risks.

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

  • Studies on discovery all types of adducts that might be biologically important if not repaired properly, or persistently exist in the pathways to affect cancer risk and initiation;
  • Identification of  DNA adducts that may promote specific driver gene mutations and perform studies applying integrated adductomic approaches to stratify cancer risk;
  • Integrative research on adducts, DNA repair capacity, and environmental exposures for cancer risk identification;
  • Discovery and characterization of adducts in combination with other types of molecular signatures and images to increase sensitivity and specificity for risk identification;
  • Mechanism research of adducts as potential targets for exploratory study of precision chemoprevention;
  • Exploration of using adductome approach to study the risk of untested products, e.g., electronic cigarettes (e-cigarettes);
  • Integration of bioinformatics approaches to identifying unique adductomic profiles, sequences or patterns in target tissues for cancer risk assessment and GxE research;
  • Develop tissue or body fluid-based molecular dosimetry studies measuring chronic exposure to environmental carcinogenic agents, such as cigarette smoke or dietary aflatoxins, to cancer risk;
  • Discover and characterize a range of adducts using adductomic approaches in the context of basic research on exposures to cancer risk factors.
  • Applicable to projects intended for NIEHS support: Develop novel technology, tools, methods, and algorithms in terms of increasing the reproducibility of quantitatively measuring DNA adducts, sensitively detecting new adducts, and analyzing adductomic data;

Projects/directions that are not appropriate for this FOA include (but are not limited to) the following type of studies.

  • Studies that are not focused on the innovative basic research on adducts and adductomics.
  • Development of new animal models (however, the use of established pre-clinical animal models for basic adductomic studies is appropriate).  
  • Any clinical trials.

In addition, NOT appropriate for NCI support (but possible for NIEHS support) are projects mainly focused on technology development and/or methodological studies.

However, projects intended for NCI support may include limited efforts to improve a technology or methods, if such improvements are needed to enhance or facilitate the primary research goals of the application. For example, a project focused on adduct identification for cancer risk assessment may benefit from a newly developed (or customized) bioinformatics software designed (adapted) specifically for the analytical technique(s) to be used for adducts detection/characterizations.

Other Resources

The awardees of the companion U01 FOA will form together with the NCI an Adductomic Working Group that will provide a forum for exchange of information and sharing experiences among the investigators participating in the adductomic research. The awardees of this R01 and companion R21 FOAs will also be encouraged to participate in this Working Group.

The programs listed below are examples of other NCI- or NIEHS-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.)

Section II. Award Information
Funding Instrument

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

Application Types Allowed

New
Resubmission (but only of applications submitted in response to this FOA)

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

Direct costs are limited to $275,000 over a two-year period, with no more than $200,000 in direct costs allowed in any single year.

Award Project Period

The proposed project period must not exceed 2 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.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

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

Required Registrations

Applicant Organizations

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

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

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

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.

2. Content and Form of Application Submission

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.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Wendy Wang, Ph.D. M.Sc.
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

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

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.

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.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

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.

3. Submission Dates and Times

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

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

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

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

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information

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.

1. Criteria

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.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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? 

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?  

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?   

Additional Review Criteria

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

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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

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.

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

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

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

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons

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

Section VI. Award Administration Information
1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

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

A final 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.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-435-0714

Scientific/Research Contact(s)

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

For inquires related to environmental exposures research contact:

Daniel T. Shaughnessy, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-2506
Email: shaughn1@niehs.nih.gov

Peer Review Contact(s)

Syed Quadri, PhD
Center for Scientific Review (CSR)
Telephone: 301-435-1211
Email: q3u@drgpo.drg.nih.gov

Financial/Grants Management Contact(s)

Brian Iglesias
National Cancer Institute (NCI)
Telephone: 240-276-6278
Email: iglesiab@mail.nih.gov

Pamela Clark
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-541-7629
Email: evans3@niehs.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.