NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

Purpose

Human health is the product of both genetic susceptibility and environmental exposure. Many studies conducted in the past, or in the field today, have not been designed to consider the full array of environmental exposures that may affect an individual's health and wellbeing. The National Institute of Environmental Health Sciences (NIEHS) intends to promote the characterization of the exposome (including chemical, physical, and biological stressors as well as lifestyle and social environments) through the establishment of an infrastructure to enable the measurement and integration of environmental exposures. The proposed Human Health Exposure Analysis Resource (HHEAR) builds on the success of the Children's Health Exposure Analysis Resource (CHEAR, https://CHEARprogram.org/). The HHEAR program will continue the essential structure of CHEAR with a consortium comprised of a Coordinating Center, Data Center, and a network of Laboratory Hubs.

Working in concert, the components of HHEAR will provide access to an infrastructure for adding comprehensive exposure analysis of biological samples and linked environmental samples to existing epidemiological and clinical studies involving research focused on understanding and improving human health. HHEAR will provide a range of services including:

• expert consultation on exposure analysis, study design, and data analysis and interpretation;
• analysis of samples using state-of-the-art methods and technologies;
• a data repository and associated data science tools;
• statistical and data analytical services including support for meta- and pooled analyses; and
• support for pilot and feasibility studies.

The harmonized laboratory analysis of samples based on rigorous quality control, as well as the central data repository will enable the integration of complex exposure data across multiple studies to enhance the opportunity for data pooling or comparative analyses. In many instances this will provide the otherwise unattainable power to statistically analyze the combined contributions of multiple environmental factors on human health across a range of diseases and disorders.

Exposures measured by HHEAR will encompass the breadth of the exposome using both comprehensive targeted (hypothesis-driven) and non-targeted (discovery-driven) methods of analysis. HHEAR will expand the analyses provided by the current CHEAR infrastructure by the addition of a component focused on the analyses of environmental samples to provide greater resolution of the sources of environmental exposures. The comprehensive approach that HHEAR offers to the scientific research community will leverage new data on environmental exposures for discovery of new hypotheses and associations and promote research projects to address common challenges in research on environmental health.

The intent of the program is broad and will cover a range of epidemiological or clinical study designs. Potential users of this resource include researchers studying the influence of non-genetic factors on human health, including studies with characterization of environmental exposures that could benefit from a more extensive, exposome-scale analysis, as well as studies that currently have little characterization of exposures that would benefit from adding exposure analysis to their existing data.

Background and Rationale

There is a rich and growing body of literature arising from the environmental health research community demonstrating that consequences of environmental exposures, particularly during critical periods in development, can manifest as disease or dysfunction at any point across the life span from infancy to old age. The original CHEAR program was explicitly focused on children as they are known to have increased risks from environmental exposures, including nutrition, stress, drugs, and environmental pollutants because their major organ systems are developing from the time of conception through adolescence. HHEAR expands this focus to include exposures occurring in other life stages and health outcomes that occur later in life to enable a life-course perspective on differing responses to the environment. Environmental health effects are complex and not simple one-to-one relationships between exposure to a single chemical entity and a single health endpoint. The comprehensive combination of data provided by HHEAR will facilitate an understanding of the complicated interactions between the multiple environmental and other factors as determinants of health.

The HHEAR infrastructure will facilitate the harmonization of data across studies by providing a focused infrastructure for comprehensive exposure analysis of biological and environmental samples including (1) rigorous assessment of a range of environmental exposures and (2) statistical tools and data science approaches to manage and analyze these newly generated datasets in a cohesive and integrated manner.

Specific Research Objectives

This FOA will support the creation of one component of the HHEAR Exposure Assessment Laboratory Network, supporting comprehensive analytical services focused on untargeted analysis of simultaneous measurement of hundreds to thousands of exogenous and endogenous compounds in biological samples that are indicative of the environmental exposures that individual has experienced. The intent of untargeted analysis is to expand the current understanding of the exposome and facilitate the discovery of novel associations between exposure and health outcomes, which can then be tested in follow-up, hypothesis driven, studies.

Untargeted analysis will complement targeted analysis of specific exposure biomarkers with simultaneous measurement of large sets of analytes including both exposure biomarkers and endogenous changes in response to environmental exposure. It is an expectation, although not a requirement, that all samples submitted to HHEAR for targeted analysis will also be analyzed with untargeted methodologies. Researchers utilizing the HHEAR Lab Network services may also request untargeted analysis without utilizing the targeted analysis services although it is encouraged as a cross-validation activity.

The Untargeted Analysis Laboratories will be comprised of three required components, described below:

• An Untargeted Analysis Resource
• A Developmental Core
• An Administrative Core

Untargeted Analysis Resource: Services provided by this resource can include, but are not limited to:

• Mass spectrometry- and NMR (as appropriate)-based global analyses of biological samples;
• Metabolite identification and annotation utilizing both in-house physical reference standard libraries and public databases that have been specifically enriched for inclusion of biomarkers of environmental exposure;
• Application of statistical analyses to support comparative analysis of spectra stratified by available supporting information such as high and low exposure groups, case-control studies, or extremes in phenotypic or clinical measures.

It is anticipated that the majority of analyses will be conducted on either urine or blood (serum or plasma as appropriate); however, a variety of additional specimen types may be needed or appropriate (such as feces, saliva, tissue extracts, or others).

To accomplish these goals a laboratory must include, at a minimum, the following:

• The equipment and protocols necessary to perform proposed untargeted analysis of biological samples with appropriate sensitivity;
• Metabolomic data analysis and interpretation tools;
• A comprehensive sample tracking and laboratory information management system; and
• Quality assurance/quality control methods, standardized measurements and reporting. Participation in round robin activities or other inter-lab collaborative studies is a plus.

In addition to the central focus on providing untargeted analytical services, each Hub will support a Developmental Core to expand the capabilities of HHEAR by developing and validating new untargeted, exposomic, exposure measures and to investigate the use of a range of accessible biological samples for human health studies. The activities of an Untargeted Lab Hub and coordination of those activities with the broader HHEAR consortium will be managed through a required administrative core.

Developmental Core: This activity will expand the research capabilities and capacity of the Hub by developing and validating new methods for future analytic services (note that these are examples and are not required). Examples of the types of activities that might be performed can include but are not limited to:

• Development of strategies for identifying the chemical identity of peaks of interest, including MSn fragmentation, and compound and standard synthesis;
• Expanding in-house library and standards to increase the number of compounds that can be identified;
• Developing novel methods or separation techniques to maximize detection of exogenous analytes;
• Developing novel methodologies and protocols for improved untargeted analysis in easily accessible biological samples in addition to serum, plasma, and urine; and
• Developing protocols and methodologies that enable inter-platform data comparison and harmonization.

Administrative Core: Each Hub will have an Administrative Core that will coordinate all activities of the lab Hub including:

• Consulting with potential clients on sample requirements, sample quality, typical concentration ranges for specific analytes (e.g., from NHANES or published literature) and the ability to identify features in untargeted analyses. This can include sample collection and storage protocols for maximizing biological information, and sample shipping;
• Support submission, analysis, and interpretation of Hub generated data in cooperation with the Data Center;
• Integration with Coordinating Center, other Hubs and Data Center; and
• Track sample handling and support quality assurance practices and data flow coordination.

See Section VIII. Other Information for award authorities and regulations.

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 not allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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

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

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

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

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

The letter of intent should be sent to:

Leroy Worth, Jr., PhD
Telephone: 984-287-3340
Fax: 301-480-3722
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (Use for the Administrative Core)	6
Core (Use for the Developmental Core)	6
Research Resource (Use for the Untargeted Analysis Resource)	12

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required, maximum 1
• Administrative Core: required, maximum 1
• Developmental Core: required, maximum 1
• Untargeted Analysis Resource: required, maximum 1

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Other Attachments:

The filename provided for the attachment will be the name used for the bookmark in the application image. Each of the four required Other Attachments must not exceed 10 pages. Applications that do not include all four attachments or exceed the page limit for one or more attachment will not be reviewed.

The following materials are required:

Library of Reference Standards (use the file name: "Library") including:

• Detail your in-house library of chemical standards specifying chemical class or analyte panel and whether the chemical is considered an endogenously produced compound or a biomarker of exposure (including chemical, physical, and biological exposures as well as nutrients, pharmaceuticals and drugs of abuse);

Analytical Platforms and Sample Capacity (use the file name: "Capabilities") including:

• Detail each available untargeted platform which will be utilized in the Resource and for each detail the appropriate biological matrices, annual sample capacity available to the Hub, and the range of exposure markers that will be detectable on the platform in complex biological media.

Quality Assurance and Proficiency Testing (use the file name 'Quality Metrics') including:

• Summary description of laboratory quality assurance and quality control procedures;
• Documentation of participation and performance in laboratory benchmarking activities such as round robin activities or cross-lab collaborative studies.

Past Performance as a service facility (use the file name 'Past Performance') including:

• Demonstration of past performance of untargeted analytical services applied to epidemiological studies through contracts or collaborations, including a description of sample types, sample volumes, sample number, and unequivocal compound identifications reported as well as publications resulted from the service if applicable.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Outline the overall goals of the proposed Untargeted Exposure Analysis Laboratory including the specific aims of the Untargeted Analysis Resource and the proposed Development and Administrative Cores.

Research Strategy: Thoroughly address the main objective of the Untargeted Exposure Analysis Laboratory, which is to create a research resource that will provide analytic services and support for exposomic analysis in biological samples derived from studies focused on human health.

The application must describe the planned organizational structure under which the Laboratory proposes to operate. An organizational chart showing how the group will function as a service facility should also be included.

As part of this section, describe the following elements:

Background, referring to the Other Attachments as necessary describe:

• How the proposed Hub will meet the general program objectives as an untargeted analytical resource;
• Untargeted analysis services to be offered and the appropriate biological matrices that will be supported;
• Strategy and work flow for chemical identification and annotation;
• Past performance as an analytical services support facility applied to epidemiological studies through contracts or collaborations; and
• Approaches to quality control and assurance and past performance in round robin or cross-lab collaborative activities.

Overview of the vision analytical Lab, including:

• Plans for moving towards a more comprehensive capability for measuring a diverse range of exogenous and endogenous exposures in studies of environmental health;
• Plans for integrating with other components of HHEAR including the targeted analysis and environmental analysis lab hubs as well as the data center to move towards a more comprehensive capability for exposomic analysis; and
• Plans for long-term sustainability of the analytic services (outreach, expanding capabilities, methods development and discovery).

Letters of Support: Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants. For program activities to be conducted off site, i.e., at an institution other than the applicant institution, a letter of assurance or comparable documentation, signed by the collaborator as well as the off-site institutional officials, must be submitted with the application.

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan addressing the following:

• The HHEAR Program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication, both in other HHEAR supported projects and by other exposure assessment, children's health and environmental epidemiology researchers. In addition, the HHEAR Program expects the sharing of study data from both the laboratory network and data and statistical resource in a timely manner, and with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Thus, the HHEAR Program expects awardees to implement a Resources and Data Sharing Plan consistent with achieving these program goals. The final Resources and Data Sharing plan will be developed by the HHEAR steering committee post award.
• In addition, the HHEAR Program encourages sharing of resources that are developed or modified to accomplish aims of this program. This may include, but is not limited to, software, tools, or protocols.
• The goals of software sharing under this program include 1) terms that permit the dissemination and/or commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages; and 2) terms of software availability that include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with others. If software is developed with support from this program, awardees and their sub-contractors are expected to implement software sharing plans consistent with achieving the goals of this program.

The application is also expected to describe plans for:

• Ensuring that data accumulated at Data Center and CC are distributed to other relevant resources in a standard data format; and
• Ensuring that the data accumulated under the Data Center and CC are made publicly available as appropriate to privacy protection agreements and can be retrieved through multiple methods of querying, including simple web interfaces for common standard queries and tools to allow the access to large datasets.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Hub PD/PI must serve as the Administrative Core Lead and should emphasize experience and expertise in coordinating multi-project programs and facilitating research linking exposure science and epidemiology.

Applicants must provide a detailed budget, including justification for all expenditures, for the Administrative Core.

Budget forms appropriate for the specific component will be included in the application package.

The budget for the Administrative Core should include travel for the Hub PD/PI and resource directors and core leads to attend annual Steering Committee and Grantee Meetings. The budget should also include costs associated with internal communications as needed.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Identify general objectives planned for the Administrative Core along with the main benchmarks that would indicate the accomplishment of these objectives.

Research Strategy: The Administrative Core will provide overall administrative and organizational oversight and management of the Hub including coordinated activity with other HHEAR grantees.

As part of this section, the applicant should address the following:

Overall Hub leadership and personnel capacity that may include but is not limited to the following:

• Administrative, operations, and support staff;
• Business and/or legal expert staff;
• Other staff required to support the Research Resource as a whole.

Detailed plans to support the activities of the Hub including at a minimum:

• Client Services and Project Management, including;

o Plans for coordination of Lab Hub consulting on Client Requests for Service and applications;

o Tracking Client Project progress within the Lab Hub; and

o Coordinating with HHEAR Data Center and Clients on analysis and interpretation of data as needed.

• Support for internal evaluation and self-assessment, including:

o Generation of Hub progress and budget reports;

o Assessing and anticipation of client needs; and

o Monitoring process efficiency and timelines for Lab Hub analyses including prioritizing and incorporating improvements into Hub operations.

• Operations management, including:

o Ability to ensure efficient and effective day-to-day administrative operations of the Lab;

o Coordination with other HHEAR Components (Hubs, Coordinating Center and Data Center); and

o Participation in outreach and promotional activities related to HHEAR.

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

Resource Sharing Plans are expected and they are discussed in the Overall component of this FOA.

Appendix:

Limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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 a 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.

Delayed Onset Study

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

When preparing your application, use Component Type Core.

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

SF424 (R&R) Cover (Developmental Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Developmental Core)

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

Research & Related Other Project Information (Developmental Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Developmental Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Developmental Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

The Senior and Key Personnel should emphasize experience and expertise in bioanalytical chemistry and biomonitoring, clinical chemistry, and/or biochemistry, toxicology, exposure science, and biomarker development and testing.

Budget (Developmental Core)

Applicants must provide a detailed budget, including justification for all expenditures, for the Developmental Core.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Developmental Core)

Specific Aims: Identify general objectives planned for the Developmental Core along with the main benchmarks that would indicate the accomplishment of these objectives.

Research Strategy: The Developmental Core will provide support for developing new methods and strategies to expand the ability of untargeted analysis to characterize the exposome in biological samples.

As part of this section, the applicant should address the following:

How the proposed Core will integrate the diverse expertise of the applicant team to meet the goals of the Hub.

Applications should describe detailed plans for the proposed Developmental Core which may include:

• Developing methods and strategies for compound identification for peaks of interest;
• Development of new sample collection, and separation methods for maximizing biological information, especially signals of low-abundance exogenous analytes;
• Development of novel approaches for performing untargeted analysis in easily accessible tissues in addition to serum, plasma, and urine; and
• Development of protocols and methodologies that enable inter-platform data comparison and harmonization.

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

• Resource Sharing Plans are expected and they are discussed in the Overall component of this FOA.

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Developmental Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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 a 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.

Delayed Onset Study

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

When preparing your application, use Component Type Research Resource .

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

SF424 (R&R) Cover (Untargeted Analysis Resource)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Untargeted Analysis Resource)

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

Research & Related Other Project Information (Untargeted Analysis Resource)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Untargeted Analysis Resource)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Untargeted Analysis Resource)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Resource Director' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

The Senior and Key Personnel should emphasize expertise and experience in:

• Metabolomics, bioanalytical chemistry and biomonitoring, clinical chemistry, and/or biochemistry, toxicology, exposure science, and application of metabolomics in the context of population studies;
• Sample tracking, workflow, and quality control for analytical services; and
• Data processing needed for interactions with Data Center and with the study investigators.

Budget (Untargeted Analysis Resource)

Applicants must provide a detailed budget, including justification for all expenditures, for the Research Resource Component.

Budget forms appropriate for the specific component will be included in the application package.

The costs associated with the Untargeted Analysis Research Resource should represent a minimum of 70% of the total Direct Costs of the Hub. These costs include the provision of analytical services at no cost to the external clients.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Untargeted Analysis Resource)

Specific Aims: This Resource will provide the technical infrastructure for untargeted analysis of biological samples to understand the broad range of environmental stressors humans are exposed to and their potential effects. Applicants should outline specific aims to address these goals.

Research Strategy: This Resource is intended to serve as a resource to the research community by providing scientific and technical expertise to researchers seeking to expand exposure assessment in their research or clinical settings. Applicants must outline the technical functions of the Untargeted Analysis Resource. The Resource will be organized around the technical work (analysis methods, protocols, data management and harmonization required to support the exposure assessment networks).

As part of this section, the applicant should address the following:

How the proposed Resource will integrate the diverse expertise of the applicant team to meet the overall goals of the Hub.

Applications should describe detailed plans for the proposed Untargeted Analysis Resource which may include:

• Description of proposed methods to be used to understand the exposome including both metabolites indicative of endogenous processes and environmental exposures. This may reference tables of in-house library/standards and platform capacity provided in "Other Attachments" of the Overall description;
• Discussion of plans for data processing, metabolite identification, annotation and reporting;
• Discussion of internal workflow oversight including quality control and analysis;
• Description of plans for harmonization of methods and analyses with other HHEAR Hubs including the potential for Round Robin and Ring Trial assessments; and
• Discussion of how the Untargeted Analysis Resource will use the required Administrative Core for its functions including interactions with the Administrative Core and the Developmental Core, including the coordination of efforts and lines of responsibilities.

Customer support capacity that may include the commitment to and plans for expert consultation on the appropriateness of selected measures for the outcomes and biological samples available from the client study should also be discussed.

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

• Resource Sharing Plans are expected and they are discussed in the Overall component of this FOA.

PHS Human Subjects and Clinical Trials Information (Untargeted Analysis Resource)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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 a 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.

Delayed Onset Study

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

Appendix: Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

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.

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) using ASSIST or other electronic submission systems. 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.

This initiative is not subject to intergovernmental review.

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

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

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NIEHS, 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

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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

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

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

Does the Hub address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the Hub 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?

Is the proposed Hub needed to achieve the goals of the environmental health research community it proposes to serve? Will coordinated services offered facilitate or expedite research that would be delayed or infeasible if conducted as independent projects? What advantages will the Hub bring to the research community? Does the proposed plan describe a laboratory Hub that will provide extensive and efficient analytical measures of exposure and response to researchers examining human health? Are future directions and needs of the research field addressed with appropriate consideration to adapting or modifying new measures of environmental, lifestyle and other non-genetic factors for studies of human health?

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

Do the PD(s)/PI(s) and other personnel have appropriate experience and training, and have they demonstrated an ongoing record of excellence in supporting community-wide research projects? Are the investigator's experience and expertise with analytical services, assay development, and processing of relevant biological samples from epidemiological studies appropriate? Is the investigator's experience in developing and validating novel approaches to exposure assessment well documented?

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?

Does the application propose novel organizational concepts, management strategies, or instrumentation in providing services to the environmental health research community? Are the concepts, strategies, or instrumentation novel to the application of exposure assessment in health research or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed? Are novel approaches being used by the investigators to adapt or develop new methods for measuring analytes that reflect exposures to environmental and lifestyle factors in health studies? Does the proposed plan allow for novel, validated methods to be incorporated into the Untargeted Analysis Resource during the project period?

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

If the Hub 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?

Are the overall design, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research community the Hub will serve? Does the proposed plan create a sufficiently high likelihood of successful adaptation and scale-up of existing methods for adoption by diverse health focused studies? Will the proposed effort support the integration of targeted and untargeted exposure assessment?

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?

Are the existing instrumentation and expertise adequate for continued support and expansion of the laboratory Hubs? If additional instrumentation dedicated to the project is needed, can this be acquired rapidly and within the budget for immediate use in the laboratory Hub? Are there sufficient commitments of facilities, infrastructure, and other resources to allow for the full-scale operation throughout the project period?

As applicable for the Hub 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.

Quality Control, Assurance, and Proficiency testing

Is the plan for quality assurance and control and demonstrated performance through laboratory benchmarking activities such as round robin activities or cross-lab collaborative studies appropriate to the overall analytical scope and proposed capabilities of the Hub? Is the commitment to quality control and proficiency testing demonstrated in the Hub's previous performance as a service-oriented facility?

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

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.

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable

As applicable for the Hub 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.

Not Applicable

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

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

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.

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

Review Criteria for Administrative Core

Reviewers will provide an overall score for the Administrative Core, in consideration of the following review criteria. Individual criterion scores will not be assigned.

Reviewers will specifically assess the likelihood that the proposed resources and oversight by this Core will provide and exert a sustained, effective, influence in the field of environmental health. Consideration of the following bullets should also be included in the overall assessment:

• Is a well-reasoned and appropriate strategy for managing and coordinating Hub activities and providing administrative support for the activities of the Developmental Core and the Untargeted Analysis Resource described?
• Has the application provided an appropriate strategy for coordinating activities with the other laboratories and integration with the Data Center, and Coordinating Center, and for providing technical information to study investigators on sample collection, storage and/or processing information for obtaining maximum information on analytes from biological samples?
• Does the Hub Director demonstrate an ongoing record of accomplishments related to the objectives of the Core?
• Has the Administrative Core provided an appropriate plan for internal evaluation and self-assessment, including: the ability to generate Hub progress reports, the ability to assess and anticipate researcher needs; and the ability to prioritize and incorporate improvements into Hub operations that enhance its utility for providing additional data and analyses for environmental health studies?
• Will the Administrative Core benefit from unique features of the scientific or administrative environment or collaborative arrangements?

Review Criteria for Development Core

Reviewers will provide an overall score for the Development Core, in consideration of the following review criteria. Individual criterion scores will not be assigned.

Reviewers will consider the following in determining overall merit of the Development Core. An application does not need to be strong in all categories to be judged likely to have major scientific impact

• Are the Core Lead and other staff well suited for the Core? Has the Core Lead demonstrated an ongoing record of accomplishments related to the objectives of the core?
• Does the Development Core enhance the ability of the Untargeted Analysis Resource to utilize novel approaches or methodologies to measure analytes or biological markers reflecting environmental exposures?
• Does the application provide a well-reasoned and appropriate strategy for improving the ability of exposomic analysis by increasing the number of potential exposure biomarkers and analytes measured in untargeted analysis?
• Has the applicant provided a sound strategy for applying metabolomics in accessible biological samples beyond serum, plasma, or urine?
• Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core proposed? Will the Development Core benefit from unique features of the scientific environment or collaborative arrangements with other components of the laboratory?

Review Criteria- Untargeted Analysis Resource

Reviewers will evaluate the following resource and provide an overall score based on the individual review criteria for each required resource. Individual criterion scores will not be assigned.

Reviewers should consider the individual bulleted elements in their overall assessment in terms of scientific and technical merit, and in providing overall impact score:

• Do the investigators provide appropriate complementary expertise in metabolomics, exposomics, and other analytical methods for untargeted (global) metabolite analysis for exogenous and endogenous compounds?
• Is the existing infrastructure sufficient to support the planned activities or are plans to acquire and install new equipment appropriate?
• Does the research strategy adequately address in sample tracking, workflow, and quality control to provide the required analytical services to study investigators?
• Do the investigators have experience with peak identification and compound identification for discovery and measures of new analytes associated with exposure and disease?
• Are data processing and coordination with the Data Center adequate for transferring analytical data to the data repository?
• Do the investigators provide expertise in analysis and processing of global metabolite data needed for interactions with other Resources within the laboratory Hub, with the Data Center and with the study investigators?
• Does the Resource Director provide a plan to ensure efficient and effective day-to-day administrative operations of the Untargeted Analysis Resource?

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the National Institute of Environmental Health Sciences 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 National Advisory Environmental Health Sciences Council. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. 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. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. 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 http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 75, and other HHS, PHS, and NIH grant administration policies.

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

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

The PD/PI (or multiple PDs/PIs, if applicable) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and report back results, interpretations, and conclusions of projects conducted. The PD/PI assumes responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the HHEAR component in accordance with terms and conditions of the award.

All PD(s)/PI(s) of HHEAR components (Laboratory Network, Data Center, and Coordinating Center) will have the primary responsibility for:

• Defining objectives and approaches for HHEAR and its components;
• Overseeing the planning, budgeting and conducting of all HHEAR scientific, organizational, and administrative activities specific to the PD(s)/PI(s)'s specific award as well as sharing information with other HHEAR awardees to facilitate such activities among the other HHEAR components;
• Promoting, coordinating, and participating in scientific collaborations and approaches across HHEAR components;
• Promoting, coordinating, or participating in collaborations between HHEAR and external investigators, including active participation in consultations, data sharing, and collaborative research projects with investigators using the HHEAR infrastructure;
• Overseeing or participating in the training of external investigators using HHEAR (including prospective users);
• Establishing agreements amongst themselves and NIH staff that address the following issues:
• Providing goals and estimated costs for analyses;
• Policy and procedures for transferring data among HHEAR components and external investigators;
• Establishing and adhering to data and metadata standards and sharing data, protocols, and other research resources generated by HHEAR components;
• Procedures for safeguarding confidential information, including data generated by HHEAR components as well as information and/or data received from external investigators;
• Policy and procedures for addressing ownership of intellectual property that result from aggregate multi-party data; and
• Policy and procedures for reviewing publications and determining authorship
• Ensuring training of HHEAR personnel as needed for standardization of collaborative protocols across components and for accurate and timely data entry. Participating in quality evaluations including round-robin and formal proficiency testing assessments.
• Overseeing improvements in HHEAR infrastructure; including the incorporation of methods developed within the Laboratory Network Hubs into other HHEAR activities.
• Ensuring adherence to the approved plans for timely sharing of resources and data amongst HHEAR components as well as with external investigators using the HHEAR infrastructure;
• Overseeing or participating in dissemination and outreach activities to promote use of HHEAR to the scientific community;
• Facilitating the formation of and participating in appropriate Working Groups, such as but not limited to exchange of protocols, emerging technologies, data standards, QA/QC;
• Participating as voting member(s) in the activities of the HHEAR Steering and Executive Committees and interacting with any sub-committee(s);
• Complying with Coordinating Center requests, as directed by NIH Program Staff and the Executive Committee, to facilitate monitoring of HHEAR progress.
• Attending and participating in the annual PD/PI scientific meetings, and regular committee calls organized by the HHEAR Coordination Center, as relevant
• Accepting and implementing all scientific, organizational, administrative, and policy recommendations approved by the HHEAR Executive Committee to the extent consistent with applicable grant regulations;
• Cooperating in the program evaluation process and interacting with NIH representatives and the Scientific Expert Panel coordinating this process;
• Overseeing the timely preparation and submission to the NIH of progress reports and other information as needed;
• Conducting periodic self-evaluation of the resource; and
• Being prepared for administrative site visits by NIH staff members.

The PD/PI responsible for the HHEAR Coordinating Center will have the following additional responsibilities:

• Organizing the development of HHEAR Steering and Executive Committees and other HHEAR sub-committees;
• Organizing and providing logistical support for Steering and Executive Committees, Working Groups and other sub-committees;
• Budgeting for, organizing, and providing logistical support for the annual HHEAR Scientific Meeting and annual in-person Steering Committee meeting;
• Identifying, collecting, and managing relevant protocols, data, and other resources used by the HHEAR components;
• Overseeing a "Pilot and Feasibility" program, with significant input from NIH Program Staff and the HHEAR Steering Committee, to support new emerging technologies or pilot data collection; and
• Serving as the Chair for the Steering and Executive Committees, which at a minimum includes setting agenda, compiling monthly minutes and quarterly summaries in coordination with NIH staff.

Intellectual Property Considerations:

Awardees will be responsible for relevant intellectual property oversight that will include:

• Ensuring the ability to maintain, manage, modify, and distribute items and instruments by securing appropriate permissions from other parties involved;
• Ensuring that infrastructure, items, and instruments developed with NIH grant support are made available to users in a manner consistent with NIH sharing policies (see http://sharing.nih.gov), including the NIH research systems policy and the NIH data sharing policy as applicable;
• Ensuring that agreements with any party, including users, do not unreasonably limit access by other parties to the HHEAR infrastructure and/or items or instruments; and
• Establishing appropriate agreements between/among stakeholders for the appropriate sharing of data and appropriate protection of intellectual property.
• The PD(s)/PI(s) assumes responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of research conducted with or through HHEAR in accordance with terms and conditions of the award.

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

One or more designated NIH staff, acting as Project Scientist(s), will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. If more than one Project Scientist is identified on any HHEAR component, one will be assigned as the Lead Project Scientist. The NIH Project Scientist(s) and other substantially involved NIH program staff members will assist HHEAR by:

• Monitoring the operations of HHEAR components and activities;
• Evaluating the progress and compliance of HHEAR with the operating policies of the Steering Committee;
• Attending and participating in all Steering Committee and subcommittee meetings of the HHEAR program;
• Along with the Coordinating Center, organizing and coordinating annual HHEAR Scientific meeting;
• Participating in the HHEAR evaluation activities, including coordination of an external evaluation of the HHEAR Program;
• Evaluating the adherence of HHEAR awardees to any approved data sharing plans or intellectual property plans;
• Serving as a liaison between the Steering Committee, HHEAR, NIH and other federal or international agencies as needed;
• Making recommendations to the HHEAR Steering Committee on strategic directions and improvements to HHEAR components and activities;
• Serving as a liaison to facilitate and/or coordinate interactions between HHEAR and other entities that may be mutually beneficial;
• Using the NIH channels to disseminate knowledge about the HHEAR to scientific community and other stakeholders as needed; and
• Facilitating contacts between HHEAR and non-HHEAR-affiliated researchers interested in potential collaborations with the HHEAR and/or the use of the HHEAR as a resource.

NIH staff members who are substantially involved in the scientific activities (e.g., publications) of the HHEAR will not attend peer review meetings of renewal and/or supplemental applications.

In addition, an NIH Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the award, and will be named in the award notice. If this individual becomes substantially involved in the HHEAR activities, he/she will not attend peer review meetings of renewal and/or supplemental applications or will seek NIH waiver if such participation is essential.

The NIH reserves the right to adjust funding, withhold, suspend, or terminate the support to the HHEAR awardee and/or member institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance.

Areas of Joint Responsibility include:

HHEAR Steering Committee.

The HHEAR Steering Committee will serve as the main body for deliberation for the HHEAR Program including discussion of current and prioritization of future activities. As a deliberative body the Steering Committee is intended to provide consensus recommendations to the HHEAR Executive Committee.

The Steering Committee will consist of the following voting members:

• HHEAR PD(s)/PI(s);
• Up to two additional designees from each HHEAR component; and
• The NIH Program Officer(s) and Project Scientists for each HHEAR Component.

The HHEAR Steering Committee may also form subcommittees, each with a specific functional area of oversight as defined in the application. Members of Steering Committee subcommittees need not be voting members of the Steering Committee.

The PD/PI of the Coordinating Center will serve as Steering Committee Chair the first year of the program; thereafter, a Steering Committee Chair will be elected every twelve months from amongst the Steering Committee members by the committee. An individual may continue serving as Chair for more than one year if all committee members agree. NIH staff cannot serve as Steering Committee Chair.

The Steering Committee will meet via webconference on a regular schedule determined collectively by the group with approval from the Executive Committee. The Steering Committee will meet in-person at least once per year at a date and location determined by the Executive Committee.

HHEAR Executive Committee.

The HHEAR Executive Committee will serve as the main decision-making body for the HHEAR Program. The HHEAR Executive Committee will meet via webconference on a regular schedule agreed by the members and at in-person meetings of the HHEAR Steering Committee. Additional in-person meetings of the Executive Committee may be held at the request of NIH Program Directors or other members by majority vote.

The HHEAR Executive Committee will have primary responsibility for:

• Overseeing the overall functioning of the HHEAR;
• Reviewing HHEAR strategic goals for its evolution as a research resource (in consultation with Scientific Expert Panel, see below);
• Sharing progress among the components of the HHEAR; and
• Ensuring that the HHEAR takes advantage of existing NIH resources and programs.

The Executive Committee will consist of the following voting members:

• HHEAR PD(s)/PI(s);
• The NIH Program Directors/Officer.

Each component of the HHEAR infrastructure will have one collective vote, including NIH Program staff. For multi-PI/PD grantees or Laboratories funded to conduct more than one analysis type, one designee will be selected to cast the collective vote of that unit.

Additional, non-voting, members of the HHEAR consortium may attend and participate in Executive Committee meetings with the assent of the group; such participants will not be voting members.

In the event that the Executive Committee cannot agree on critical aspects, such as common protocols, then NIH Staff will have final authority to implement proposed recommendations. All activities must comply with NIH, DHHS, and Federal Guidelines.

The PD/PI of the Coordinating Center will serve as Executive Committee Chair the first year of the program; thereafter, a Chair will be elected every twelve months by the committee. An individual may continue serving as Chair for more than one year if all committee members agree. NIH staff cannot serve as Executive Committee Chair

Other guidelines for the Steering and Executive Committee, such as a quorum, frequency, duration, and type of meetings (in-person, remote), will be determined at its initial meeting.

Scientific Expert Panel.

A Scientific Expert Panel will operate as an evaluative subcommittee to the NIH, advising NIH and providing technical expertise to the entire HHEAR. This panel will comprise scientific experts not affiliated with the HHEAR institutions and may include scientists from academic and other research institutions as well as from NIH, other Federal Agencies, and relevant scientific experts and stakeholders. Members of the Scientific Expert Panel will be selected by the NIH in consultation with the HHEAR Steering and Executive Committees. The Scientific Expert Panel will be charged with the following activities:

• Serving as the review and prioritization body for HHEAR client studies
• Reviewing the overall progress of the HHEAR and making appropriate recommendations to strengthen activities in certain areas as requested by NIH Staff;
• Participating in the semi-annual HHEAR Scientific Meetings;
• Providing additional consultations to the Steering and Executive Committee and NIH staff as needed (responding to inquiries via e-mail and/or telephone); and
• Providing linkages to investigators not funded by HHEAR but conducting, or interested in providing related services.

Dispute Resolution:

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

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

A final RPPR, 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.

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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and 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)

General Grants Information (Questions regarding 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]

David M. Balshaw, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3234
Email: [email protected]

Claudia L. Thompson, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3330
Email: [email protected]

Gary Ellison, Ph.D., M.P.H.
National Cancer Institute
Telephone: 240-276-6783
Email: [email protected]

Manjit Hanspal, PhD
Program Officer
Environmental Influences on Child Health Outcomes (ECHO)
Office of the Director, National Institutes of Health
Phone: 301 435 5008
Email: [email protected]

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

James Williams
National Institute of Environmental Health Sciences
Telephone: 984-287-3338
Email: [email protected]

Crystal Wolfrey
National Cancer Institute
Telephone: 240-276-6277
Email: [email protected]

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

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