Part 1. Overview Information

Key Dates

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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose:

The RIVER program is intended to fund people rather than projects; rewarding individuals from the NIEHS grantee community who demonstrate a broad vision and potential for continuing their impactful environmental health research and who are most likely to benefit from a program emphasizing flexibility and sustained support.

Overview:

RIVER is intended for investigators, regardless of career stage, who demonstrate the potential to conduct outstanding, innovative, and transformative research and articulate a clear and compelling vision for revolutionary research to advance the environmental health sciences. For this reason, eligibility is limited. Please refer to Section III. Eligibility Information for specific details.

It is expected that RIVER will improve long-term research outcomes and facilitate ambitious, creative research by providing a flexible and stable funding environment within a broad scientific domain with broadly stated 'goals' rather than specific aims and by stating the kinds of techniques that might be used to address them rather than providing specific experimental details. Key features and benefits of the program fall into two large categories: (1) freedom from traditional focused specific aims and a structured research plan which will enable investigators to pursue new directions in their research as they arise throughout the funding period, and (2) the ability to devote increased effort to research, mentoring, and scientific service due to reduced time spent writing and managing multiple grant applications and awards.

Research involving human subjects is permitted under this FOA. Specifically, mechanistic trials and/or fundamental or basic experimental studies with humans (BESH) are permitted. Phase I, II, III, and T4 clinical trials are not permitted under this FOA. BESH studies are referred to in NOT-OD-18-212 as prospective basic science studies involving human participants . These studies fall within the NIH definition of a clinical trial and also meet the definition of basic research. Types of BESH studies that fit within this FOA include studies using human subjects to support a deeper understanding of the mechanisms underlying the effects of environmental exposures on human health, including molecular epidemiological studies. See the Comparison of Funding Opportunity Types by Clinical Trial Allowability table for additional guidance.

RIVER is intended to support the majority of an individual's independent research program; as such, the R35 award will require a relinquishment and consolidation of projects funded by NIEHS at the time the R35 is issued and dedication of at least 6 person months (i.e., the equivalent of 50% effort on a full-year appointment, 66.67% on a 9-month appointment, or 100% on a 6-month appointment) of the PD/PI's total effort to the project throughout the R35 award. NIEHS scientific program and grants management staff will review this information in relation to Other Support prior to award to ensure sufficient level of effort is committed to the project and to ensure no commitment overlap. Commitment overlap occurs when an individual's time commitment exceeds 100% (i.e., 12 person months), whether salary is requested in the application.

Some types of grant awards will be excluded from consolidation, such as:

• Research that, by its nature, is focused on a specific aim or is dependent on the priorities of NIEHS or other investigators:
  • NIEHS solicited programs (RFAs, PARs, and select PAs)
  • Multi-PD/PI research projects
  • Clinical/Interventional Trials
  • Small Business awards
• Research that is not funded by the NIEHS, including projects that are administered by NIEHS but are funded by other ICs or Agencies.
• Efforts that are not focused on Environmental Health Research goals:
  • Training/Career Development awards (Institutional or individual)
  • Conference Grants

The NIEHS will not consider investigator-initiated applications from current R35 awardees until the final year of their award. It is anticipated that the RIVER program will be evaluated on a continuing basis by the NIEHS, to assess the impact of the program on the portfolio of the NIEHS, and on the progression of the awardees' careers. Metrics to be used include, but are not limited to: publications, including numbers, impact factors, citations of publications; academic promotion of the PD/PIs; invited talks at national/international symposia; students and postdoctoral fellows trained in the PD/PI's laboratory; honors and awards received by the PD/PI; committee service of the PD/PI; and subsequent grant support awarded. The Program Analysis Branch of the Division of Extramural Research and Training will determine the design of the program evaluation. PD/PIs awarded RIVER grants will be requested to provide information for the evaluation during the period of the award.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not 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) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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.

Only single PD/PI applications are allowed. Applications with multiple PD(s)/PI(s) will not be accepted. Applications that do not meet eligibility requirements will not be reviewed.

Eligibility is determined by NIEHS after the receipt of applications on the intended application due date. Eligibility to apply to this FOA is limited to those individual PD/PIs who meet all of the following criteria:

• Is currently the PD/PI on at least one single investigator (i.e., not Multi-PD/PI) NIEHS-supported R01-equivalent (defined here as R01, DP1, DP2, or DP5) award that meets all of the following requirements:
  • Be a single-PD/PI award, AND
  • Has been supported by NIEHS for 4 years (i.e. active at the time of application and in Fiscal years 2017, 2018, and 2019 potentially including up to 1 year of no-cost extension within this period), AND
  • Not be an NIH-defined clinical trial, unless that clinical trial meets the definition of a mechanistic clinical trial or a BESH trial, as defined in Section I of this FOA.

Because of the highly selective nature of the program, RIVER requires a Letter of Recommendation from a peer working in a similar domain of the environmental health sciences as well as a Letter of Support from the applicant Institution.

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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:

Leroy Worth Jr., PhD
National Institute of Environmental Health Sciences
Telephone: 984-287-3340
Fax: 301-480-3722
Email:[email protected]

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

Applicants are required to devote at least 6 person months (i.e., the equivalent of 50% effort on a full-year appointment, 66.67% on a 9-month appointment, or 100% on a 6-month appointment) of their effort throughout the R35 award. This requirement pertains to total support and includes all financial resources, whether Federal, non-Federal, commercial or institutional, available in direct support of an individual's research endeavors, including but not limited to research grants, cooperative agreements, contracts, and/or institutional awards. Training awards, prizes or gifts are not included.

Specific Aims: Do not use. Specific Aims are not required and must not be submitted.

Research Strategy: The Research Strategy is expected to evolve over the duration of a RIVER award; therefore, a detailed experimental plan is not expected and should not be included. The Research Strategy should focus on general scientific themes and approaches to be taken to address broad but critical questions within the area of study/and or related to the goals of your research program.

The Research Strategy should contain the following sections:

1. Background:

• Provide a brief background of the area(s) of environmental health science research proposed and key scientific questions or challenges which will be addressed.
• Describe the potential for the identified area(s) of research to be groundbreaking, paradigm-shifting, or transformative and the future impact on the environmental health sciences.
• Discuss the potential ways this work may impact human health and describe how the R35 project might evolve through different phases of the environmental health translational research process (https://ehp.niehs.nih.gov/doi/10.1289/ehp3657). Depending on the field of study, provide detail on how the research will enable novel therapeutic targets, develop novel strategies and approaches to protect human health, inform policy, lead to changes in clinical protocols, or enable population-wide intervention/prevention efforts.

2. Evidence of transformative impact:

• In the context of the broad area which is the focus of your R35 application, describe how you will leverage your contributions of novel ideas, key scientific accomplishments, experience, high impact productivity, scientific service, or cross disciplinary collaborations in the proposed future research program. This discussion should highlight the impact of research funded by NIEHS, including groundbreaking findings from previous support. If the planned research diverges significantly from past work and the current NIEHS funded projects which will be consolidated into the R35, explain the rationale for the changes and describe your ability to undertake this new direction.
• Discuss how you will continue to maintain a trajectory of creative, groundbreaking, paradigm-shifting, or transformative research and to conduct rigorous, reproducible, and transparent research in your proposed research program. Do not repeat information adequately covered in the Biosketch.
• Provide a statement of your commitment to maintaining a central focus on the environmental health sciences and protection of human health throughout the flexible research program.

3. Overview of the future research program:

• Describe, through broadly defined goals, the research vision for your research program for the requested support period. Discuss the reasons and likelihood that the proposed research program will continue to be important and generate significant/timely new discoveries.
• Discuss, in general terms, strategies and potential outcomes including any key innovative or unique methods which will be applied in your research program. Experimental details and extensive preliminary data are not required but information may be included if it is critical in assessing overall feasibility of the initial research approach. This includes justification for work utilizing either human subjects or vertebrate animals where projections based on previous (e.g., R01) research efforts are appropriate to describe the launch point for initial investigations in the R35. Include a discussion of rigor and reproducibility and the authentication of biological and chemical resources.
• Describe how the research program could evolve as the work is being performed and how the risks and challenges will be addressed. This description should set up the temporality of the program. In general, more detail is expected at earlier time points in the research strategy.
• Describe how results from the proposed research will lead to change/progress in your field regarding practice of existing methods, development of novel technologies or therapeutic targets, policy change, or changes in public health practice.

4. Suitability of the RIVER Program:

• Explain how sustained funding, level of effort, and a flexible research approach that this mechanism enables is necessary to complete the proposed work and to achieve the realization of your research vision.

Letters of Support:

Applications must include one of each of two types of letters:

1. Letter of Recommendation: Applications must include, under Letters of Support, one Letter of Recommendation for the applicant being proposed for the RIVER Award. The Letter of Recommendation should come from a peer of the PD/PI and discuss the outstanding contributions of the applicant to the environmental health sciences and the unique qualities of this individual which make them an ideal candidate for a sustained and flexible research program. In two pages or less, the peer Letter of Recommendation should describe:

• A statement of the PD/PI's demonstrated outstanding contributions to the environmental health sciences including novel ideas, key scientific accomplishments, experience, high impact productivity, scientific service, or evidence of cross disciplinary collaborations, which are commensurate with their career stage and the potential for the PD/PI's research productivity and influence to continue at the same high caliber level; and
• A discussion of the unique qualities of the applicant which support the need for a flexible research opportunity.

2. Letter of Support: In addition, RIVER applications require a separate Letter of Support from the applicant's institution which should be signed by the person at the institution who has the responsibility to evaluate and endorse the outstanding potential contributions of the applicant to the environmental health sciences (e.g.: Department Chair, Dean, etc.) and with the authority to commit the institution to all the requirements of the application and award. The institutional Letter of Support should indicate:

• The PD/PI's commitment of at least 6 person months (i.e., the equivalent of 50% effort on a full-year appointment, 66.67% on a 9-month appointment, or 100% on a 6-month appointment of their effort throughout the R35 award (see Sections I and III.1 for further explanation);
• A willingness to support the consolidation of other support from the NIEHS into the R35 award;
• An agreement not to submit additional investigator-initiated applications listing this individual as PD/PI to the NIEHS until the final year of the R35 award; and
• A clear and continuing substantial institutional commitment to the PD/PI beyond the normal level extended by the Institution to faculty (e.g., 20% salary support, access to resources, protected time, space, etc.) for the duration of the award.

Only one Letter of Recommendation from an individual scientist and one Letter of Support from an institution is allowed; however, applicants may submit letters of commitment from collaborators as appropriate. Letters of commitment should be clearly labeled as such to distinguish them from both the Letter of Recommendation and Letter of Support.

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The plan should describe the proposed approach to data management and sharing that the specific research will employ. If certain elements of the plan have not been determined at the time of submission, an entry of "to be determined" may be acceptable if a justification is provided along with a timeline or appropriate milestone at which a determination will be made. The Data Sharing Plan should address each of the following points in detail.

• Identify the types and estimated amount of scientific data that will result from the research program, including which scientific data will be preserved and shared and the rationale for these decisions.
• Indicate whether specialized tools and/or software are needed to access or manipulate shared data to support replication or reuse and specify how the needed tools can be accessed.
• Identify standards, if any, that will be applied to the scientific data and associated metadata to be collected, including data formats, data identifiers, and other data documentation to be used.
• Describe the data preservation and access strategy, including where scientific data will be archived to ensure long-term preservation (i.e. which repositories), whether scientific data will be available through restricted or unrestricted access, and the anticipated timeframes for preserving and sharing scientific data. Use of publicly accessible data repositories is encouraged.
• Describe any data sharing agreements, licenses, and other data sharing restrictions or use limitations.
• Identify the individual(s) who will be responsible for executing the various components of data management over the course of the research program including a description of the appropriate expertise for oversight.

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute of Environmental Health Sciences, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIEHS Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The research strategy is expected to evolve over the eight-year award period; therefore, applicants should describe general scientific themes and approaches to be taken to address broad but critical questions within the area of study/and or related to the goals of the applicant's research program. Experimental details and extensive preliminary data should not be included unless they arenecessary to assess the feasibility of new avenues of research. Reviewers should evaluate whether the scope of research proposed is sufficiently comprehensive, forward-thinking, and innovative for the R35 mechanism.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the program 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 program proposed).

Significance

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

Specific to this RFA: Does the application address a critical challenge in the environmental health sciences which requires a sustained and flexible research program to overcome? Will achievement of the proposed, broadly stated goals lead to a transformation on a specific domain within the environmental health sciences or provide future direction for the environmental health sciences research field as a whole?

In addition, for applications involving clinical trials:

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the program? If the PD/PI is 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)?

Specific to this RFA: Does the PD/PI have a consistent record of productivity and significant scientific impact in the proposed field of study commensurate with the applicant's career stage that can be leveraged to continue at the same high caliber level? Has the PD/PI shown evidence of being creative, innovative, and adaptable in their research career as relevant for their specific field that indicates that this individual is likely to thrive in a research program which is not bound by specific aims and methodological details? Is the PD/PI clearly the intellectual driver of the proposed research program? Does the PD/PI demonstrate a record of professional service to the research community and successful mentoring that could be expanded upon due to reduced time spent managing multiple grant applications and awards? Does the PD/PI provide evidence of a continued commitment to embracing the ideas of rigor and reproducibility and of transparency in science including data sharing and collaboration as well as translation of science across scales of research and to diverse communities?

In addition, for applications involving clinical trials:

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

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

Specific to this RFA: How likely is it that the proposed program will result in new opportunities, explore new areas of scientific inquiry, and/or develop new systems or broadly applicable strategies? Does the application capitalize on exploration of research in creative directions within a broadly defined theme?

In addition, for applications involving clinical trials:

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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

Specific to this RFA: Has the applicant successfully integrated the goals of their existing research activities into a scientifically valid and clear approach relevant to human health? Is there a logical plan for sustained progress across the research program for the eight-year award period? Is there evidence that the research program will evolve appropriately as the work is performed? Is there an appropriate plan to use the stability and flexibility of the R35 mechanism to achieve the program goals and are the potential risks and challenges appropriately addressed? Does the application indicate appropriate commitment of time and effort for the proposed work? For epidemiology studies, is the research grounded in public health significance, where results can lead to meaningful applications in public health and clinical practice settings, design of future population-level studies, or inform policy makers and other key stakeholders in the relevant research area?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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

Environment

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

Specific to this RFA: Has the applicant institution demonstrated appropriate support for fostering a sustained and flexible research program in the Environmental Health Sciences, assuring that the investigator will be able to dedicate appropriate resources to the RIVER program? Does the application indicate a level of institutional commitment of support for the PD/PI beyond the normal level extended by the Institution to faculty?

In addition, for applications involving clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

In addition, for applications involving clinical trials:

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

• 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.

• 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

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

Section VI. Award Administration Information

1. Award Notices

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.

Research involving human subjects is permitted under this FOA. Specifically, mechanistic trials and/or fundamental or basic experimental studies with humans (BESH) are permitted. Phase I, II, III, and T4 clinical trials are not permitted under this FOA. NIH defines basic research consistent with the definition of basic research in federal code, "the systematic study directed toward greater knowledge or understanding of the fundamental aspects of phenomena or of observable facts without specific applications towards processes or products in mind."

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety

Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

2. Administrative and National Policy Requirements

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

3. Reporting

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 agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

Section VII. Agency Contacts

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:[email protected](preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:[email protected]

Jennifer B. Collins
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3247
Email: [email protected]

Kimberly Gray, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3262
Email: [email protected]

Frederick L. Tyson, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3334
Email: [email protected]

Leroy Worth Jr., PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3340
Email: [email protected]

Bryann E. Benton
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-323-5577
Email: [email protected]

Section VIII. Other Information