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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government, including the NIH Intramural Program
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations

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

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
  • Dun and Bradstreet Universal Numbering System (DUNS) Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.

• eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

• Grants.gov Applicants must have an active 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. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST 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.

2. Content and Form of Application Submission

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.

Letter of Intent

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

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

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

The letter of intent should be sent to:

D.P. Mohapatra, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Fax: 301-402-2060
Email: [email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

These above-mentioned page limits refer to the research strategy section only; a separate "Specific Aims" page for each individual component of the U19 application should be submitted in accordance with the SF424 (R&R) Application Guide Instructions.

Revision applications must include an Overall component and the components that are affected by the revision.

Overall Component

When preparing your application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Note: Proposed use (if any) of Human Embryonic Stem Cell lines and Human Fetal Tissue should be described in each relevant research projects and cores, as well as in the overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

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:

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

Facilities and Other Resources:

In this section, describe the institutional, commercial, and industrial investments and resources that constitute the environment for this research program. New cost-sharing commitments are not required. Some examples of institutional environment could include recruitment and salary support of new faculty or professional staff positions to support the resource components, startup packages, space renovations for team investigators, new facilities within the research and core components, dedicated equipment for research and resource components, dedicated budget lines or facilities for a team consortium, dedicated use of commercial products and technologies, equipment and technology contributions from commercial collaborators, etc. Summarize how the facilities and resources under each component are complimentary, and critical to the overall research goals and plan for this U19 center application. Facilities and resources specific for individual Research Projects and Cores should be detailed under the respective component sections.

• In addition to standard items, describe existing facilities and/or other resources (such as existing institutional shared resource cores) available to the proposed U19 research program and center.
• As applicable and pertinent to the proposed research, describe partnerships (e.g., with industrial entities) that will provide relevant capabilities.

Equipment:

Summarize on the availability and accessibility of all necessary equipment for the proposed U19 research program and center, and how they are complimentary and critical to the overall research goals and plan of this application. Equipment specific for individual Research Projects and Cores should be detailed under the respective research project and core sections.

Required Other Attachments:

Milestones (maximum 2 pages): Applications to this FOA must define a clear set of overall goals that are aligned with the expected PRECISION Human Pain network’s objectives and outcomes. This attachment should be entitled "Milestone Plan.pdf . Milestones must include clear, quantitative, and objective criteria for success. Annual quantitative milestones should establish feasibility for all aspects of the proposed research and provide clear indicators of continued progress or emergent difficulties and will be used to evaluate the application, not only in peer review, but also in consideration of the awarded project for funding of non-competing award years. The application must include well-defined milestones: e.g., amount and quality of data that will be generated by each data types each year, data comprehensiveness in terms of cell or tissue types, pain conditions and/or diseases, or pain conditions in the context of chronic analgesic or other drug use, etc., expected quality performance measures to be reached each year, and criteria for prioritizing selection of biospecimens and incorporation of new technologies, where applicable. Annual milestones should reflect the current ability to produce data from the beginning of the project and include plans for critically evaluating and revising these milestones on a regular basis.

Project/Performance Site Locations (Overall)

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.

Research and Related Senior/Key Person Profile (Overall)

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

In the biosketches, outline the PD(s)/PI(s) knowledge and past leadership experience in the relevant area of science. Outline his/her ability to organize, direct and administer a complex research project. Outline the Research Project and Core leaders' knowledge, past leadership experience, and past collaborative, teamwork experience.

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.

Budget (Overall)

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

A minimum total effort for the overall PD/PI or MPI of the U19 center application is 2.4 person months. Effort cannot be reduced below this level during the entire project period.

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.

PHS 398 Research Plan (Overall)

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment of the Overall Component in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe concisely the central scientific, data and resource production goals of the proposed U19 Center, and state in priority order the overall aims of the Center to generate data on molecular signatures, cell types, and cellular function phenotypes or signatures that underlie human pain signal transduction, transmission, and processing. List the titles of all Research Projects and Cores. Outline how the Research Projects and Cores will synergistically contribute to attaining the aims of the proposed U19 Center and the overall goals of the NIH HEAL Initiative’s PRECISION Human Pain network.

Research Strategy: This section provides applicants an opportunity to present conceptual wholeness and research, data and knowledge integration of the U19 Center.

• State the general issues, gaps, and challenges in the relevant human pain-associated genes, cellular function, and tissue analyses areas.
• Describe currently existing human pain-associated genes, cellular function and tissue analysis datasets and the state-of-the art approaches used.

• Provide a chart to describe the overall organizational structure of the proposed Center with an overview of the performance sites and responsibilities of the Research Projects and Cores (Note: No steps need to be taken to include an external advisory board in the applications as a PRECISION Human Pain network-wide External Scientific Panel will be established by the NIH HEAL Initiative Project Team after awards are made). Define the roles among the different entities. Include a plan for communication and coordination across entities demonstrating that the Center is integrated and capable of performing the proposed functions.
• Summarize the expertise of the multidisciplinary team, including expertise in pain biology (including human pain), high-throughput genome, proteome and metabolome experimentation and analysis, including single-cell analysis, human tissue processing, medium- and large-scale single-cell functional analysis, tissue histological and imaging analysis, bioinformatics and data science. Include evidence that the team of investigators has been or will be able to work together effectively to accomplish the research and goals of the proposed U19 Center and the PRECISION Human Pain network.
• Outline the rationale and brief research approach/plan for individual research projects and core facilities proposed.
• Describe innovative aspects of the proposed Center, including the generation of novel datasets and/or tools. Offer well-reasoned justifications for new and innovative approaches, including a discussion of feasibility. Explain how these novel data and/or tools will lead to transformative, paradigm-shifting advances in the field.
• Summarize overall goals for comprehensiveness of data to be produced by the Center.
• Highlight the overall synergy and integration across the proposed Research Projects and Cores showing the whole is greater than the sum of its parts. Discuss the interdisciplinary nature of the research components and the Cores, and how this will serve to accomplish the goals of the program in the context of related pain type(s)/indication(s) and/or disease-associated pain conditions. Include evidence for feasibility.
• Explain how the proposed Research Projects and Cores will contribute uniquely to the overall research aims of the U19 Center and the overarching goals of the NIH HEAL Initiative’s PRECISION Human Pain network.
• Describe approaches to include input from patients and caregivers from diverse communities on the goals of the project.
• Provide an overview of the consent process for human biological samples as well as a framework for considering the ethical, legal, and social implications of the design and implementation of the tissue collection efforts, and Center studies.
• Describe the appropriateness of the collected tissues for the goals of the Center, including normative tissue samples for comparison.
• Provide an overview of production workflow incorporating quality control/quality assurance measures and decision-making process. Workflow and experimental designs should ensure robust and unbiased results, which are essential for the utility of data produced by the Center.
• Describe the Center's capacity to operate at scale and provide evidence that demonstrates this capacity.
• Identify possible rate-limiting steps as it relates to workflow across different components of the Center, and include plans to address possible bottlenecks, as appropriate.
• Include a descriptive and graphic timeline for the proposed work. This section should also include specific proof-of-concept test(s).
• Provide alternative strategies, as appropriate, should any research project or core fail to perform or pass proof-of-concept test(s) as expected.

Letters of Support: Statements of individual and Institutional Commitment, as appropriate to the overall application, should be included in this section.

• Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants. Letters of support for the overall should be included with the Overall component. Letters of support for individual Research Projects or Cores should be included with those components of the application. Letters of support should indicate the specific activities the individual or organization will perform in pursuit of the Center goals; letters of support from individuals or organizations without a specific role in the Center should not be included.
• The applications are expected to include written statements from the officials responsible for intellectual property issues at all of the applicant institutions (including subcontractors) to the effect that the institution supports and agrees to abide by the resource sharing plans put forth in the application if applicable. Such letters would be clear expressions of commitment. A separate letter should be sent by each participating organization including each subcontractor. Please note that institutional sign-off on the grant application signifies that all relevant components of the institution, including the relevant office handling intellectual property matters have reviewed and approved the document.
• If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.
• If collaborating with a private entity, include a letter of support that addresses any agreement to provide agent(s), resources and/or experimental or analytical platforms; any limits on the studies that can be performed with said agent(s), resources and/or experimental or analytical platforms; any limitations on sharing of data (including negative results); and whether a licensing agreement(s) will be needed and in place once the project is funded. This letter should come from a high official within the private entity who has authority to speak and take decision on these issues.
• If an application plans to utilize the infrastructure or resources of existing projects, whether funded by NIH, other governmental or non-governmental entities, letters of support detailing the terms of collaboration and data sharing must be included.
• For procurement and utilization of biological samples and specimens in the U19 research program, letters of support or approval for use of those samples and specimens should be included.

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.

The following modifications also apply:

NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing.Consistent with the HEAL Initiative Public Access and Data Sharing Policy (https://heal.nih.gov/about/public-access-data), all applications, regardless of the amount of direct costs requested for any one year, are required to include a Data Management and Sharing Plan outlining how scientific data and any accompanying metadata will be managed and shared. The plan should describe data types, file formats, submission timelines, and standards used in collecting or processing the data. It is expected that data generated by HEAL Initiative-funded projects will be submitted to study-appropriate domain-specific or generalist repositories in consultation with the HEAL Data Stewardship Group to ensure the data is accessible via the HEAL Initiative Data Ecosystem. Additional guidance on data related activities can be found at https://www.healdatafair.org/.

To maximize discoverability and value of HEAL datasets and studies, and facilitate data integration and collaboration, applications submitted in response to this FOA are strongly encouraged to incorporate standards and resources where applicable:

• Applicants are encouraged to ensure that data collected by the study conform to Findable, Accessible, Interoperable, and Reusable (FAIR) principles.
• Applicants are specifically encouraged to incorporate into their planning, an alignment with the guidelines, principles and recommendations developed by the HEAL Data Ecosystem, including but not limited to preparing data to store in selected specified repositories, applying minimal metadata standards, use of core HEAL Clinical Data Elements (CDEs, https://heal.nih.gov/data/common-data-elements), and other necessary requirements to prepare data to connect to the HEAL Data Ecosystem.

• All new HEAL clinical pain studies are required to submit their case-report forms/questionnaires to the HEAL Clinical Data Elements (CDE) Program. The program will create the CDE files containing standardized variable names, responses, coding, and other information. The program will also format the case-report forms in a standardized way that is compliant with accessibility standards under Section 508 of the Rehabilitation Act of 1973 (29 U.S.C 794 (d)), which require[s] Federal agencies to make their electronic and information technology accessible to people with disabilities. HEAL Initiative clinical studies that are using copyrighted questionaries are required to obtain licenses for use prior to initiating data collection. Licenses must be shared with the HEAL CDE team and the program officer prior to use of copyrighted materials. For additional information, visit the HEAL CDE Program.

The NIH notices referenced below provide additional NIH guidance that should be considered in developing a strong data management and sharing plan. The list is instructive but not comprehensive.

• Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014)
• NIH has provided guidance around selecting a repository for data generated by NIH-supported research and has developed desirable characteristics for all data repositories (NOT-OD-21-016).
• NIH encourages the use of data standards including the PhenX Toolkit (www.phenxtoolkit.org) (for example, see NOT-DA-12-008, NOT-MH-15-009)
• NIH encourages researchers to explore the use of the HL7 FHIR (Fast Healthcare Interoperability Resources) standard to capture, integrate, and exchange clinical data for research purposes and to enhance capabilities to share research data (NOT-OD-19-122). The FHIR standard may be particularly useful in facilitating the flow of data with EHR-based datasets, tools, and applications.
• NIH encourages clinical research programs and researchers to adopt and use the standardized set of data classes, data elements, and associated vocabulary standards specified in the United States Core Data for Interoperability (USCDI) standards, as they are applicable (NOT-OD-20-146). Use of the USCDI can complement the FHIR standard and enable researchers to leverage structured EHR data for research and enable discovery.

Recipients conducting research that includes collection of genomic data should incorporate requirements under the NIH Genomic Data Sharing Policy (NOT-OD-14-124, NOT-OD-15-086).

Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:

Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.

• Key biological and/or chemical resources may or may not have been generated with NIH funds and: 1) may differ from laboratory to laboratory or over time; 2) may have qualities and/or qualifications that could influence the research data; and 3) are integral to the proposed research.
• These include, but are not limited to, biological and chemical reagents / tools, source, species backgrounds & modifications; positive or negative comparator cell lines, dissociation and/or culture conditions for primary cells, cell lines and primary tissue preparations; specialty chemicals, antibodies, and other biologics.
• Standard laboratory reagents that are not expected to vary do not need to be included in the plan. Examples are buffers and other common biologicals or chemicals.

Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).

Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

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

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application, use Component Type Administrative Core.

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

SF424 (R&R) Cover (Administrative 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 (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative 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) (Administrative 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 (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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.

In the biosketches, document the ability of the Core Director to organize, direct and administer a complex research project.

Budget (Administrative Core)

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

The U19 overall PD/PI(s) is/are expected to serve as a Project Lead of the Administrative Core with a minimum effort of 0.6 person months. If multiple PD/PIs serve as co-leads for the Administrative Core, eachof themareexpected to devote at least 0.6 person months.

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 (Administrative Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: State in priority order the aims of the Administrative Core to address issues of the U19 Center coordination, communication, and management, indicating how the Core will contribute to the Center’s goals, as well as to the overarching goal of the NIH HEAL Initiative PRECISION Human Pain network.

Research Strategy:

• Describe a staffing and administrative plan that includes a discussion of the structure and roles of administrative and scientific staff for the core, including individual responsibilities, the functions to be performed, and how resources will be prioritized, allocated, and managed. The description should clearly indicate the facilities, resources, services and professional skills that the Administrative Core will provide.
• Describe the Administrative Core's role in managing all aspects of the production of datasets, tools, analyses, and data management of the proposed U19 Center.
• Describe how each Research Project and Core will draw upon the Administrative Core and how it in turn will respond to Research Project or Core needs.
• Describe how the Administrative Core will ensure that all Center’s Research Projects and Cores are meeting the performance objectives and milestones, as well as any novel features of the Administrative Core that enhance the collaborative effort, including optimizing communication, decision-making and resource sharing among the Center’s Research Projects and Cores.
• Describe how the Administrative Core will support the development and implementation of standard operating procedures (SOPs); maintain fidelity to research procedures and fiscal accountability; ensure quality control (QC) for data and/or tool generation; ensure timely submission of data to the PRECISION Human Pain network’s DCIC; oversee the analyses of all data by the Data Core; and oversee the coordination with the NIH HEAL Initiative’s Public Access and Data Ecosystem.
• Describe how the Administrative Core will interact and ensure efficient cooperation, communication and coordination, and resource sharing among the NIH HEAL Initiative PRECISION Human Pain network entities to promote synergistic research efforts.
• Describe how the Administrative Core leadership will participate and coordinate with the NIH HEAL Initiative PRECISION Human Pain network Steering Committee.

Additional information required in the Administrative Core Research Strategy:

Governance Plan: Provide a detailed governance plan describing how the Team Director and a Project Manager (if proposed) will organize and direct efforts across the Research Projects and Cores. When multiple institutional sites are involved, a detailed description of the cooperative administrative arrangements should be included. Documentation of these arrangements should be included in the Overall Letters of Support section. This section should include acknowledgement of the need for quarterly reporting to the NIH HEAL Initiative program staff of the progress and accomplishments. Additional meetings with the NIH HEAL Initiative program staff will be arranged on a frequency appropriate for the development stage of the project, as determined by the NIH HEAL Initiative.

Letters of Support: Provide any letters of support from collaborators that are specific to the Administrative Core.

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:

Note: Do not submit the Resource Sharing and Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.

Appendix:

Only 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 human subjects research, clinical research, and/or NIH-defined 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

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

Human Tissue Procurement and Processing Core

When preparing your application, use Component Type Human Tissue Procurement and Processing Core.'

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

SF424 (R&R) Cover (Human Tissue Procurement and Processing 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 (Human Tissue Procurement and Processing Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Human Tissue Procurement and Processing 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) (Human Tissue Procurement and Processing 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 (Human Tissue Procurement and Processing Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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.

In the biosketches, outline the experience of personnel with human tissue procurement and processing for various downstream bulk tissue and single-cell molecular analyses.

Budget (Human Tissue Procurement and Processing Core)

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

The Human Tissue Procurement and Processing Core Lead(s) must commit to a minimum of 0.6 person months of effort.

Budgets are also required for each consortium (subcontract), if they are part of the Human Tissue Procurement and Processing core.

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 (Human Tissue Procurement and Processing Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: State in priority order the aims of the Human Tissue Procurement and Processing Core, indicating how this core will contribute to the proposed goals of the U19 Center, as well as to the overarching goal of the NIH HEAL Initiative PRECISION Human Pain network.

Research Strategy:

• Describe tissue processing approaches utilized in currently existing transcriptome, cell function, proteome, metabolome, and histological/imaging analysis datasets on human pain.
• State the general issues, gaps, and challenges in the relevant human pain-associated tissue procurement, processing, and analysis for harmonized data collection, analysis, and reporting for cross-comparison and rigorous validation.
• Describe a staffing and operation plan that includes a discussion of the structure, roles and responsibilities of scientific and technical staff for the core, including the functions to be performed, and how resources will be prioritized, allocated, and managed. The description should clearly indicate the facilities, resources, services and professional skills that the Human Tissue Procurement and Processing Core will provide for the Research Projects and Resource Cores.
• Outline the rationale and research approach/plan for the proposed Human Tissue Procurement and Processing Core.
• Describe prior experience and/or plans to collaborate with organ procurement organizations and medical examiners to facilitate donor recruitment. Describe plans for donor screening and recruitment along with a proposed timeline for the acquisition of biospecimens.
• Describe plans for developing consent forms for broad data sharing without any identifying subject information.
• Provide details on data collection (clinical, phenotypic and associated metadata) using acceptable data collection standards.
• Describe plans for developing and implementing standardized and uniform approaches and quality control measures. Highlight any innovative aspects of the proposed protocols, procedures, and/or tools for the procurement and processing of human pain-associated tissue. Offer well-reasoned justifications for new and innovative approaches, including a discussion of feasibility.
• Describe a process for monitoring quality, quantity, and appropriateness of the collected tissues, establishment of SOPs, MTAs (where applicable), and informed consent documents.
• Describe how the Human Tissue Procurement and Processing Core will conduct and coordinate with such cores from other U19 centers in the PRECISION Human Pain network to develop and optimize experimental protocols in the context of specific experimentation and analysis types for:
  • Extraction and processing of human tissues associated with pain signal transduction, transmission, and processing
  • Dissociation and cell sorting
  • Fixation and processing of tissue for histological and imaging analysis
  • Dissociation and cultures of primary human neuronal and non-neuronal cells and co-cultures with ganglionic non-neuronal cell types
  • Preparation of SC and brainstem slices

• Include evidence for feasibility, including any supporting general and background preliminary findings.

• Describe how this core will coordinate with other U19 centers to disseminate resources related to optimized protocols and procedures for human pain-associated tissues to pain research communities.

• Describe how each of the Research Project(s) and Core(s) of the U19 Center will draw upon the Human Tissue Procurement and Processing Core, and how it in turn will respond to Research Project or Core needs. Include a timeline as well as a description of plans for appropriate stabilization, suitable storage and rapid shipment of biospecimens as needed by the Center’s Research Projects and Cores.

Letters of Support: Provide any letters of support from collaborators that are specific to the Human Tissue Procurement and Processing Core.

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:

Do not submit Resource Sharing or Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.

Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:

Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.

• Key biological and/or chemical resources may or may not have been generated with NIH funds and: 1) may differ from laboratory to laboratory or over time; 2) may have qualities and/or qualifications that could influence the research data; and 3) are integral to the proposed research.
• These include, but are not limited to, biological and chemical reagents / tools, source, species backgrounds & modifications; positive or negative comparator cell lines, dissociation and/or culture conditions for primary cells, cell lines and primary tissue preparations; specialty chemicals, antibodies, and other biologics.
• Standard laboratory reagents that are not expected to vary do not need to be included in the plan. Examples are buffers and other common biologicals or chemicals.

Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).

Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.

Appendix:

Only 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 (Human Tissue Procurement and Processing Core)

When involving human subjects research, clinical research, and/or NIH-defined 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

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

Data Core

When preparing your application, use Component Type Data Core.

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

SF424 (R&R) Cover (Data 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 (Data Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data 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) (Data 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 (Data Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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.

Budget (Data Core)

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

The Data Management Core Lead(s) must commit to a minimum of 0.6 person months of effort.

Budgets are also required for each consortium (subcontract) if they are part of the data core.

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 (Data Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: State in priority order the aims of the proposed Data Core, indicating how the core will contribute to the proposed goals of the U19 Center as well as to the overarching goal of the NIH HEAL Initiative PRECISION Human Pain network.

Research Strategy: Explain how the Data Core will serve the proposed U19 Center. Provide an overview as well as a detailed plan on data management and analysis practices.

• Describe database infrastructure and plans for information management and monitoring, management of complex multimodality data, statistical analysis and inference of biological mechanisms, data integration and registration to a common tissue and cell coordinate systems, and computational modeling if appropriate.
• Propose data analysis methods and procedures for the Center including analysis algorithms and data hierarchy.
• Describe how the data core will provide bioinformatics expertise, data integration and analysis support, and study design and statistical support/services to project investigators.
• Provide statistical rationale about data quality and informatics analysis about data novelty.
• Describe and offer evidence for the feasibility of the proposed data management plan, the advantages of any new data management methodologies, the potential pitfalls and alternative approaches for data management, and how these might impact the overall progress of the U19 Center’s research objectives and the goals of the network.
• Propose and justify data/metadata standards and formats to be used while demonstrating flexibility for adopting different ones.
• Describe plans for maintaining records for biospecimen procurement and associated metadata elements in close collaboration with the Tissue Procurement and Processing Core.
• List and define the data and metadata to be shared with other PRECISION Human Pain U19 Centers and describe how the Data Core will ensure timely submission of data and data analyses to the network’s Data Coordination and Integration Center (DCIC).
• For shared data, propose when it will be made available, where it will be stored, how it will be maintained, and how others will be able to find, access, and reuse it. Note that funded U19 Centers will be required to share data in accordance with agreed-upon standards for the NIH HEAL Initiative PRECISION Human Pain network, and NIH HEAL Initiative Public Access and Data Sharing division

Letters of Support: Provide any letters of support from collaborators that are specific to the Data Core.

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:

Do not submit Resource Sharing or Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.

Appendix:

Only 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 (Data Core)

When involving human subjects research, clinical research, and/or NIH-defined 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

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

Resource Core

When preparing your application, use Component Type Resource Core.

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

SF424 (R&R) Cover (Resource 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 (Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Resource 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) (Resource 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 (Resouce Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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.

Budget (Resource Core)

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

Resource Core Lead(s) must commit to a minimum of 0.6 person months of effort.

Budgets are also required for each consortium (subcontract) if they are part of any resource core.

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 (Resource Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: State in priority order the aims of the proposed Resource Core, indicating how the core will contribute to one or more of the Research Projects and Cores of the U19 Center. Provide a concise description of the broad activities and services of the proposed Core. Indicate why the Resources Core is an essential part of the U19 application, and how the proposed services will facilitate accomplishment of the proposed goals of the U19 Center and of the PRECISION Human Pain network

Research Strategy: Explain how the Resource Core will contribute to the research activities for one or more Research Projects and Cores of the U19 Center. Note: Resource Cores should not duplicate resources already available at the institution. Also, the activities of Resource Cores must not overlap with each other or with the activities of a Research Project(s) and/or of other Cores.

• Describe the facilities, services and/or types of resources that will be provided and managed, and how they will meet the specific needs of each Research Project and/or Core. Include a prioritization plan for providing the services and/or resources, and plans for quality control.
• State the rationale for centralizing activities in a Resource Core rather than including them in individual Research Projects.
• If one of the Core’s objectives is to improve technologies, tools, and or reagents, describe limitations and gaps of the current technologies and tools in throughput, sensitivity, selectivity, scalability, spatiotemporal resolution and reproducibility in tissue, cells and gene analyses. Propose improvements that will address the current limitations and gaps, and how said improvements, if achieved, will enhance the goals of the U19 Center as well as the overarching goals of the network.
• Describe the unique and innovative contributions that will be made by this Resource Core.
• Describe the advantages of any new resource types and methodologies, the potential pitfalls and alternative approaches, and how these might impact the overall progress of the U19 Center’s research goals.
• Where appropriate, describe how the Resource Core will facilitate dissemination of technology, expertise, materials, experimental models or modalities, and potential collaborations with other members of the U19 Center as well as across all network centers.
• Describe the role(s) of the Resource Core Lead and key participants without duplicating information provided in the Biosketches or the Budget Justification.
• If the Resource Core is at a different geographic location than the Research Projects and Cores it serves, describe plans for data/material(s) transfer and communication.
• Describe any plans for collaborations or contracting for specific services to outside facilities (academia and/or industry), with justification. Corresponding letters of support/service should be included in the Letters of Support section below.

Letters of Support: Provide any letters of support from collaborators that are specific to the Resource Core.

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:

Note: Do not submit the Resource Sharing and Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.

Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:

Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.

Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).

Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.

• Key biological and/or chemical resources may or may not have been generated with NIH funds and: 1) may differ from laboratory to laboratory or over time; 2) may have qualities and/or qualifications that could influence the research data; and 3) are integral to the proposed research.
• These include, but are not limited to, biological and chemical reagents / tools, source, species backgrounds & modifications; positive or negative comparator cell lines, dissociation and/or culture conditions for primary cells, cell lines and primary tissue preparations; specialty chemicals, antibodies, and other biologics.
• Standard laboratory reagents that are not expected to vary do not need to be included in the plan. Examples are buffers and other common biologicals or chemicals.

Appendix:

Only 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 (Resource Core)

When involving human subjects research, clinical research, and/or NIH-defined 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

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

Research Projects

When preparing your application, use Component Type Research Project.

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

SF424 (R&R) Cover (Research Project)

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 (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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.

Facilities and Other Resources:

In this section, describe the institutional, commercial, and industrial investments and resources that constitute the environment for this research program. New cost-sharing commitments are not required. Some examples of institutional environment could include recruitment and salary support of new faculty or professional staff positions to support the resource components, startup packages, space renovations for team investigators, new facilities within the research and core components, dedicated equipment for research and resource components, dedicated budget lines or facilities for a team consortium, dedicated use of commercial products and technologies, equipment and technology contributions from commercial collaborators, etc. Summarize how the facilities and resources under each component are complimentary, and critical to the overall research goals and plan for this U19 center application. Facilities and resources specific for individual Research Projects and Cores should be detailed under the respective component sections.

• In addition to standard items, describe existing facilities and/or other resources (such as existing institutional shared resource cores) available to the proposed U19 research program and center.
• As applicable and pertinent to the proposed research, describe partnerships (e.g., with industrial entities) that will provide relevant capabilities.

Equipment:

Summarize on the availability and accessibility of all necessary equipment for the proposed U19 research program and center, and how they are complimentary and critical to the overall research goals and plan of this application. Equipment specific for individual Research Projects and Cores should be detailed under the respective research project and core sections.

Project /Performance Site Location(s) (Research Project)

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 (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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.

Budget (Research Project)

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

The PD/PI is expected to devote a minimum effort of 1.8 person months. If multiple PD/PIs serve as co-leads for this research component, they are expected to devote a combined minimum effort of 1.8 person months

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 (Research Project)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: State in priority order the aims of the proposed Research Project, indicating how the project will contribute to the U19 Center’s objectives as well as to the overarching goal of the PRECISION Human Pain network to generate data on molecular signatures, cell types, and cellular function phenotypes or signatures that may underlie human pain signal transduction, transmission and processing, including, but not limited to specific pain types, conditions and/or diseases, and/or under conditions of chronic analgesic use, other drug use, SUDs and other co-morbid and/or overlapping pain conditions. Provide a concise description of the rationale for the specific aims and questions proposed, and the overall approach to address the goals of the research project.

Research Strategy:

1. Significance

• Describe the overall objective(s) and the impact of the proposed research project towards the overall goals of the U19 Center as well asthe overarching goals and expected outcomes of the PRECISION Human Pain network.
• Provide a comparative view of other/existing data pertaining to similar questions and coordinates on molecular signatures, cell types, and cellular function phenotypes or signatures that underlie human pain signal transduction, transmission and processing and the state-of-the art approaches used.
• Summarize how the proposed research and data outcomes would generate data on molecular signatures, cell types, and cellular function phenotypes or signatures that underlie human pain signal transduction, transmission and processing.
• Explain the contribution(s) of this research project to the overall goals of the U19 Center and how it will interact with and benefit from other Research Projects and Cores. Explain how these contributions will be made possible by team synergy beyond the otherwise independent components of the Center.
• Provide the rationale for the specific goals of the Research Project, in relation to the overall goals of the U19 Center.
• Provide a clear outline of the preliminary data supporting the rationale for the proposed research project.
• Describe the overall strengths, weaknesses, and rigor of the preliminary data, including the data in published studies that are used to support the rationale for the proposed studies.
• Address potential shortcomings of the research plans, and strategies for dealing with them.
• Provide preliminary data and/or evidence in support of the proposed interdisciplinary nature and collaborative team-based approach for rigorous generation of data on human pain-associated molecular signatures, cell types, and cellular function phenotypes or signatures.
• Describe the unique contribution of experts in the multidisciplinary team to the goals of this Research Project.

2. Innovation

• Describe the unique and innovative contributions that will be made by this research project with regards to questions, tools, and approaches to generate novel datasets on human pain-associated molecular signatures, cell types, and cellular function phenotypes or signatures.

3. Approach

• Describe the data and resource production and research themes, and the type and condition (in relation to pain and associated conditions) of human tissue samples and structures/regions to be analyzed.
• Define comprehensiveness or breadth and depth for the proposed project, describing how close to that target the proposed project will get in a five-year time frame for each data element being investigated.
• Address how the proposed experimental design will ensure that the data generated are rich in content and spatially annotated on a common neural tissue and cell atlas for the dissemination and use by the broad research community.
• Describe production workflow including throughput as well as rate-limiting steps. Provide plans for assessing and improving this pipeline, where applicable.
• Describe scalable methods with preliminary data and case studies to support their feasibility of generating high-quality data in a cost-effective manner.
• Provide current estimates of data quality and plans for how data quality will be evaluated during the course of the project. Describe quality control/quality assurance measures and decision-making processes.
• Describe plans to assure a rigorous experimental design for data and sample collection, analytical methods, statistical analysis or deconvolution of data leading to the generation of core datasets. Please refer to https://grants.nih.gov/policy/reproducibility/guidance.htm for guidance on NIH policy on enhancing reproducibility through rigor and transparency. Also, please refer to https://grants.nih.gov/policy/reproducibility/resources.htm for resources on preparing a rigorous application.
• Provide a plan to ensure appropriate standardization of assays, samples, data, and controls that will be used for this research project. Propose plans to coordinate with other research components and cores on these aspects.
• Describe and offer evidence for the feasibility of the proposed experiments, the advantages of any new methodologies, assays, outcome measures, analytical/statistical models, and the potential pitfalls and alternative approaches for the research project. Also, describe how these might impact overall progress of the research project and goals of the center.
• Discuss plans (if any) for collaborations with outside resources (academic facilities, contractors and/or industry), other than the Resource Cores in this U19 application.

Letters of Support: Provide any letters of support from collaborators that are specific to the Research Project.

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:

Note: Do not submit the Resource Sharing and Data Sharing Plans here. The Resource Sharing and Data Sharing Plans should be submitted only in the Overall component.

Authentication of Key Biological and/or Chemical Resources: Individuals are required to comply with the instructions for authentication plans for key biological and/or chemical resources as provided in the SF424 (R&R) Application Guide, with the following modification:

Briefly describe methods to ensure the identity and validity of key biological and/or chemical resources used in the proposed studies.

• Key biological and/or chemical resources may or may not have been generated with NIH funds and: 1) may differ from laboratory to laboratory or over time; 2) may have qualities and/or qualifications that could influence the research data; and 3) are integral to the proposed research.
• These include, but are not limited to, biological and chemical reagents / tools, source, species backgrounds & modifications; positive or negative comparator cell lines, dissociation and/or culture conditions for primary cells, cell lines and primary tissue preparations; specialty chemicals, antibodies, and other biologics.
• Standard laboratory reagents that are not expected to vary do not need to be included in the plan. Examples are buffers and other common biologicals or chemicals.

Information in this section must focus only on authentication of key biological and/or validation of key resources to be used in the study; all other methods and preliminary data must be included within the page limits of the research strategy. See NOT-OD-16-011 and NOT-18-228 for detailed information on authentication of key biological and/or chemical resources. Applications identified as non-compliant with this limitation will be withdrawn from the review process (see NOT-OD-17-105).

Reviewers will assess the information provided in the Authentication of Key Biological and/or Chemical Resources section. Any reviewer questions associated with key biological and/or chemical resource authentication will need to be addressed prior to award.

Appendix:

Only 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 (Research Project)

When involving human subjects research, clinical research, and/or NIH-defined 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

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) 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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. 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 unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

Applications Involving NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided to the NIH Intramural Program, not through the extramural awardee's institution. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

Post Submission Materials

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.

Section V. Application Review Information

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

A meritorious U19 application is expected to be well-balanced in interdisciplinary science that spans expertise in pain biology, including human pain, high-throughput genome, proteome and metabolome experimentation and analysis, including single-cell analysis, human tissue processing, medium- and large-scale single-cell functional analysis, tissue histological and imaging analysis, bioinformatics, statistics, and data science. In addition, the proposed number and composition of Research Projects and Cores are expected to adequately reflect the overall theme(s) of the Center and requirements of the PRECISION Human Pain network to achieve its goals

The entire research application will receive one Impact Score based on critical consideration of all the components of the entire application. To guide the final scoring, reviewers will make interim assessment scores of the Overall and each Research Project (scores 1-9), and each Core (exceptional, adequate, or inadequate).

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

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

Significance

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

Specific to this FOA:

• Do the proposed aims and scientific questions align well with the overarching goals and the expected outcomes of the NIH HEAL Initiative PRECISION Human Pain network?
• Are the expected results likely to provide substantial data related to the comprehensive discovery and characterization of functional genetic elements, epigenetic signatures, molecular/cellular functions and pathways, and neural circuits that underlie human pain transmission and processing?
• Will successful completion of the aims lead to transformative advances in the field, including but not limited to the mechanistic understanding and enhanced translation of therapeutics for multiple human pain conditions?

Investigator(s)

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

Specific to this FOA:

• Is the team diverse, collaborative and multidisciplinary, such that it is comprised of appropriate content experts recognizable as leaders in their field?
• Does the team include adequate expertise in pain biology (including human pain), high-throughput genome, proteome and metabolome experimentation and analysis, including single-cell analysis, human tissue processing, medium- and large-scale single-cell functional analysis, tissue histological and imaging analysis, bioinformatics and data science?
• Has the proposed PD(s)/PI(s) demonstrated extensive knowledge, experience, and leadership in the proposed research area, with a strong record of scientific achievements? Has the proposed PD(s)/PI(s) demonstrated her/his ability to organize, direct, and administer a complex research topic?
• Have the leaders of individual Research Projects or Cores demonstrated knowledge, experience, and leadership in their respective Research Projects and Cores? Are there prior demonstrations of collaborative teamwork?
• Is there evidence that the research team has been/will be able to work together effectively to accomplish the research proposed in the projects?
• Has adequate leadership for day-to-day project management activities been described?

Innovation

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

Specific to this FOA:

Note: Since this FOA specifically seeks applications to systematically generate human pain-associated genes, cellular function and tissue analysis datasets, and possibly related tools, the NIH expects that some applications may propose mature and well-established approaches that may not be innovative per se to produce robust high-quality datasets for broad use by the research community.

• Does the application describe evidence that demonstrates the novelty of the human pain-associated genes, cellular function and tissue analysis data and tools to be generated?
• Will the novel data and/or tools lead to transformative, paradigm-shifting advances of the field?

Approach

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

Specific to this FOA:

• Will experimental designs ensure that rigorous, high-quality human datasets will be generated?
• Does the application adequately describe and discuss experimental designs to ensure the data quality and comprehensiveness?
• Does the application demonstrate the Center's capability to operate at scale as proposed?
• Does the application provide evidence of how production goals are set and can be attained?
• Is synergy between individual research components and cores interdisciplinary and adequate to accomplish the individual and overall goals of the proposed program, in the context of related pain type(s)/indication(s) and/or disease-associated pain conditions?
• Is the timeline reasonable for the work proposed?
• Are plans to include input from patients and caregivers provided and appropriate?
• Have the applicants conveyed appropriate considerations for consent processes and ethical, legal, and social implications of Center activities and relevant data production?
• How appropriate are the normative tissues that will be collected for comparison purposes?
• Does the application adequately demonstrate an effective workflow and describe workflow assessments?
• Are rate-limiting steps identified and appropriately addressed? Are plans included for improving the pipeline, if needed, adequate?
• Does the application provide current estimates of data quality and plans for how data quality will be evaluated during the course of the project?
• Are the Data Sharing plans adequate? Do they address how the applicants will ensure rapid release of data, including metadata, in a way that will be useful to the community?
• Does the application adequately describe how the center will closely work with the NIH HEAL Initiative’s Data Ecosystem (https://heal.nih.gov/data/heal-data-ecosystem), to maximize sharing and dissemination of datasets and digital resources to the pain research and therapeutics development communities.

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

Environment

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

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

Overall Coordination

Does the center as a whole serve a purpose to be greater than the sum of the individual Research Projects and Core components? Does the overall organizational chart clearly present an overview of the performance sites and responsibilities of the Research Projects and Cores? Are the roles clearly defined and divided among the different entities? Is there a clear and sound plan for communication and coordination across entities demonstrating an integrated Center project capable of performing the functions specified in the FOA?

Milestones

Are proposed milestones clear and quantitative? Do the milestones establish feasibility for all aspects of the proposed research? Does the application include plans for critically evaluating and revising milestones on a regular basis? Are there additional key experiments that need to have milestones? Will the milestones provide adequate information to evaluate yearly progress of the Center project as a whole?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Does the application adequately address the issues related to the public release of data and data analyses (see the rationale for FAIR (Findability, Accessibility, Interoperability, and Reusability) Data Principles)? Does the application adequately describe for shared data, when it will be made available, where it will be stored, how it will be maintained, and how others will be able to find, access, and reuse it? Does the application adequately describe specific plans for resource sharing and distribution in the application?

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

Center Components

Individual Center Components (i.e., Research Projects and Cores) will be assessed for relevant strengths and weaknesses in the context of the Overall Center; Research Projects will receiveindividual criterion scores (1-9), whereas and each Core will be assessed as exceptional, adequate, or inadequate.

Scored Review Criteria Research Project(s)

Significance

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

Specific to this FOA:

• Are the objectives of the Research Project in line with the overarching goals and expected outcomes of the NIH HEAL Initiative PRECISION Human Pain network?
• Are the expected results likely to provide significant and comprehensive data related to the discovery and characterization of functional genetic elements, epigenetic signatures, and molecular/cellular pathways that underlie human pain signal transduction, transmission, and processing?
• Will the results further the molecular- and cellular-level understanding of heterogeneity, pathogenesis, and susceptibility to specific human pain conditions, including conditions of chronic analgesic or other drug use, substance use disorders (SUDs) and other co-morbid and/or overlapping pain conditions?
• Will the approach, results, and accomplishments of the Research Project contribute to the overall goals of the center, and will it interact with and benefit from the other Research Projects and/or Cores of the Center?

Investigators

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

Innovation

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

Specific to this FOA:

• Does the application adequately summarize prior effort in generating data and tools and the remaining gaps and challenges, and thereby demonstrating the novelty of human pain-associated genes, cellular function and tissue analysis datasets that will be generated?
• Will the novel human pain-associated genes, cellular function and tissue analysis data and tools lead to transformative, paradigm-shifting advances of the field?

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

• Does the application adequately describe and discuss experimental designs to ensure data quality, content, and comprehensiveness?
• Does the application adequately provide a rationale and supporting data on the adequacy of tissue and cell sampling?
• Will experimental designs ensure high-quality human pain-associated genes, cellular function and tissue analysis datasets will be generated?
• Does the application demonstrate the Center's capability to operate at scale as proposed?
• Does the application provide evidence for how production goals are set and whether they can be attained?
• Does the application present sufficient preliminary data of high rigor and reproducibility standards, to support feasibility of the proposed scalable methods and adequate throughput?

• Does the application adequately demonstrate an effective workflow?
• Does the application describe workflow assessments and proposed improvements?
• Are rate-limiting steps identified and appropriately addressed? Are plans included for improving the pipeline adequate?
• Does the application provide current estimates of data quality and plans for how data quality will be evaluated during the course of the project?
• Are the proposed approaches of the Research Project unique and/or complementary to other Research Projects and/or Cores of the Center?

Environment

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

Scored Review Criteria Administrative Core

• Is the administrative plan appropriate to ensure the Center will meet the performance objectives and milestones? Does the application adequately describe the organizational structure and individual responsibilities? Are the Administrative Core Lead and key personnel well-qualified?
• Does the application adequately describe how the Administrative Core will respond to the unique needs of each Center component (Research Project(s) and Cores)?
• Does the application adequately describe administrative plans for: developing and implementing standard operating procedures (SOPs); maintaining fidelity to research procedures and fiscal accountability; ensuring quality control (QC) for data and/or tools generation; timely submission of data to the network’s Data Coordination and Integration Center?
• Does the application propose how the Administrative Core will create and implement administrative and leadership mechanisms that will foster effective interactions, cooperation, communication and coordination, and resource sharing with other PRECISION Human Pain network PDs/PIs and institutions to promote synergistic research efforts?
• Does the application propose how the Administrative Core leadership will participate and coordinate with the network’s Steering Committee?
• Has the proposed Team Director demonstrated her/his ability to organize, direct, and administer a complex research project?
• Is the proposed governance plan reasonable?

Scored Review Criteria Human Tissue Procurement and Processing Core

• Does the application describe how the Human Tissue Procurement and Processing Core will contribute to the proposed research and dataset generation goals of the Center, as well as to the overarching goals of the PRECISION Human Pain network?
• Does the application adequately describe the organizational structure and individual responsibilities of this core?
• Are the Human Tissue Procurement and Processing Core Lead and key personnel well-qualified? Does the team have adequate expertise and experience with human tissue procurement and processing for various downstream bulk tissue and single-cell molecular analyses?
• Are plans for donor screening and recruitment adequate to provide sufficient biomaterials to the Center’s Research Projects?
• Have the applicants adequately described plans for developing consent forms for broad data sharing?
• Does the application adequately describe plans for developing and implementing standard operating procedures (SOPs) and monitoring and ensuring quality control (QC) for human pain-associated tissue procurement and processing?
• Does the application describe how the Core will conduct and coordinate with its counterpart at other Centers in the network to develop and optimize experimental protocols for: extraction and processing of human tissues; dissociation and cell sorting; fixation and processing of tissue for histological and imaging analysis; cultures and co-cultures of neuronal and non-neuronal cells cell types; and preparation for SC and brainstem slices, towards specific experimentation and analysis types, as well as their dissemination to pain research communities?
• Did the application adequately describe how each Research Project and Core will draw upon the Human Tissue Procurement and Processing Core and how it, in turn, will respond to Research Project or Core needs?
• Does the application include evidence for feasibility, including any supporting general and background preliminary findings, as well as describe the rigor of those preliminary findings?
• What is the likelihood that the proposed strategy will result in a high quality biospecmens being available to the Research Projects in accordance with the proposed timelines?

Scored Review Criteria Data Core

• Is the data management and analysis plan appropriate to facilitate attainment of the objectives of the proposed Center?
• Does the application adequately describe data management, integration, and analysis, as well as feasibility?
• Are the Core Lead and key personnel well-qualified?
• Is the plan for data registration to a human neural atlas and/or common neural tissue coordinate system adequate?
• Does the application propose and justify standards and formats of the data, metadata, data analysis, and statistical methods?
• Are there appropriate data infrastructure(s) and pipeline(s) to support data sharing?
• Are there adequate plans for providing bioinformatic and statistical support to project investigators?
• Are there adequate plans for maintaining records for biospecimen procurement and associated metadata elements in close collaboration with the Tissue Procurement and Processing Core?
• Does the application adequately describe how the data core will:
  • Contribute to the overall progress of the Center and the goals of the PRECISION Human Pain network?
  • Share the data and metadata with the network’s Data Coordination and Integration Center (DCIC) as well as the other Centers?
  • Coordinate with the HEAL Data Ecosystem to maximize sharing and dissemination of datasets to the pain research and therapeutics development communities.

Scored Review Criteria Resource Core(s)

• If a Resource Core(s) is/are proposed, is the Core essential to advance the objectives of the proposed Center and the overall outcomes of the PRECISION Human Pain network?
• Does the application clearly describe the facilities, services and/or types of resources that will be provided and/or managed by the Core and how they will meet the specific needs of each Research Project and/or Core(s)?
• Are sufficient justifications provided in the application for centralizing activities in a Resource Core rather than including them in individual Research Projects?
• Does the application adequately describe limitations and/or gaps of the current resources and/or technologies and tools in terms of throughput, sensitivity, selectivity, scalability, spatiotemporal resolution and reproducibility within the context of human pain-associated genes, cellular function, and tissue?
• If improvements are proposed, are they adequately described? Will they address the current limitations and gaps to enhance the goals of the Center and overall network?
• Are the Core Lead and key personnel well-qualified?
• Are there adequate plans for prioritization of resources as well as quality control?
• Does the application describe how the Core will facilitate dissemination of technology, expertise, materials, experimental models or modalities, and potential collaborations with other members of the Center as well as across the network?

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NINDS, 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 will receive a written critique.

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.

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Programmatic balance. The purpose is to develop a network with complementary capabilities towards generating a comprehensive human pain genes and cells network. Therefore, decisions about awards will consider the mix of capabilities offered by the proposed centers.

3. Anticipated Announcement and Award Dates

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

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in theNIH 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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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.

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

Prior Approval of Pilot Projects

Awardee-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation.

• The recipientinstitution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The recipientinstitution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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

Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution's specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

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

• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2 CFR Part 200, 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 recipientsis 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 recipientsfor the project as a whole, although specific tasks and activities may be shared among the recipientsand the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibilities as described below:

• Define the details for the project within the guidelines of this FOA.
• Oversee and perform the scientific activities.
• Administratively manage the Center grant.
• Accept close coordination, cooperation, and participation of NIH HEAL Initiative program staff in the scientific, technical, and administrative management of the PRECISION Human Pain network. Inform the NIH program official of all major interactions with other members of the Steering Group.
• Provide milestones and cost for the Center operation to the NIH HEAL Initiative program staff as requested (usually at the outset of the award and annually thereafter, but also at other times as requested by the program staff).
• Use human pain-associated tissue samples, common neural tissue coordinate systems, and standard nomenclature to generate and integrate the data, metadata, and knowledge.
• Demonstrate capability and flexibility for modifying human neural tissue regions of study, data formats and metadata.
• Ensure that the products of the production effort meet the quality standards.
• Share data and resources according to the data release and resource sharing policies developed for and by this project as appropriate and consistent with achieving the goals of the PRECISION Human Pain network program.
• Fully disclose algorithms, software source code to the other members of the Network for the purpose of scientific evaluation.
• Not disclose confidential information obtained from other members of the Network.
• Submit data for quality assessment and/or validation in any manner specified by the Steering Committee, the External Scientific Panel, and/or the NIH HEAL Initiative program to ensure scientific rigor;
• Adhere to NIH policies regarding intellectual property and other policies that might be established during the course of this activity. Awardees will retain custody of and have primary rights to the data and resources developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Participate in PRECISION Human Pain network activities, including periodic meetings to report the Center’s progress, and coordinate publication of research results.
• Coordinate and collaborate with other U.S. and international groups that may be generating relevant human pain-associated genes, cellular function and tissue analysis datasets;
• Serve as a member of the PRECISION Human Pain network Steering Committee.
• Submit periodic progress reports as agreed upon by the Steering Committee.
• Accept and implement the common guidelines and procedures approved by the Steering Committee, External Scientific Panel, and NIH.

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

• A Program Officer will be assigned to this award. The Program Officer will be responsible for normal scientific and programmatic stewardship and guidance for the overall project within the NIH HEAL Initiative and will ensure that the generation of human pain-associated genes, cellular function and tissue analysis datasets and resources that are relevant to the diverse research community served by the NIH Institutes and Centers. The Program Officer will be responsible for milestone negotiations to ensure that the milestones are achieved and goals are being met. In addition, the NIH Program Officer is responsible for monitoring and implementing the NIH Data Sharing Plan (http://grants.nih.gov/grants/policy/data_sharing/index.htm), as well as the NIH HEAL Initiative Public Access and Data Sharing requirement - https://heal.nih.gov/about/public-access-data. The NIH Program Officer may attend Coordinating Group meetings as a non-voting participant. The NIH Program Officer will be named in the award notice.
• One or more extramural NIH program staff member may be assigned as the Project Scientist(s) for this award. The same person may serve as the Project Scientist for multiple HEAL Initiative awards. The Project Scientist(s) may interact scientifically with the PDs/PIs and other named personnel of that award, as a partner in the research, including providing technical assistance, advice, and coordination for the PRECISION Human Pain network and its component parts. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the PRECISION Human Pain network Steering Committee and that NIH staff will be given the opportunity to offer input to this process. One NIH Project Scientist will participate as a member of the Steering Committee and will have one vote.
• An NIH HEAL Initiative PRECISION Human Pain network Project Team will be composed of Program Officials and other relevant extramural staff from NIH Institutes and Centers and the Project Scientist(s). Its primary role is to ensure that the datasets and resources generated represent the diverse interests of the participating NIH Institutes and Centers, advise on human pain-associated genes, cellular function and tissue analysis datasets, resources, and activities relevant to their individual Institute/Center mission, monitor overall progress, attend Steering Group meetings as required, and report back to the NIH HEAL Initiative, as well as their Institute/Center.
• The NIH HEAL Initiative PRECISION Human Pain network Project Team will establish an External Scientific Panel (ESP) to help evaluate the progress of the PRECISION Human Pain network.
• NIH intramural scientists involved in the PRECISION Human Pain network will have the same rights and responsibilities as the comparable extramural scientists involved in the PRECISION Human Pain network. An intramural scientist may not receive salary, equipment supplies, or other remuneration from awards resulting from this FOA. The intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. The participation of an intramural scientist is independent of and unrelated to the role of the NIH Project Scientist(s). The involvement of intramural scientists needs to be consistent with NIH Policy. http://sourcebook.od.nih.gov/ethic-conduct/ethical-conduct-toc.htm

Areas of Joint Responsibility include:

PRECISION Human Pain network Steering Committee:

The Steering Committee will be composed of the PD(s)/PI(s), Project Scientist(s) and External Scientific Panel members (experts to be named after award). The Steering Committee may also include designated representatives from the HEAL Data Sharing Ecosystem, as appropriate. The Steering Committee will be established to help monitor progress, encourage improvements, and coordinate the production of human pain-associated genes, cellular function and tissue analysis datasets and resources through the PRECISION Human Pain network. It is anticipated that additional coordination mechanisms might be set up with other U.S. and international groups that may join this effort. The PRECISION Human Pain network Steering Committee members will meet periodically to plan and design activities, review, and discuss progress, and establish priorities and policies. A chair will be designated on a rotating basis as needed. Each PD(s)/PI(s), and external scientific advisor will have one vote each and the NIH will have one vote through the participation of the Project Scientist(s). The frequency of meetings will be determined by the Project Scientist(s) who will be responsible for scheduling the time and place and for preparing concise proceedings or minutes which will be delivered to the Steering Committee members within 30 days after the meeting. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

The PRECISION Human Pain network Steering Committee will:

• Discuss progress in meeting the research community's need for human pain-associated genes, cellular function and tissue analysis datasets and resources.
• Facilitate the development of uniform procedures and policies, for example for data standards, quality measures and assessment, nomenclature, and annotation conventions for data depositions, and so forth.
• Recipient members of the Steering Group will be required to accept and implement the common guidelines and procedures approved by the Steering Group.
• Coordinate and improve human pain-associated genes, cellular function and tissue analysis datasets data production, for example by reporting progress, disseminating best practices and collectively evaluating new procedures, resources, and technologies.
• Establish subcommittees as needed to address particular issues. Subcommittees will include representatives from the PRECISION Human Pain network, the NIH HEAL Initiative PRECISION Human Pain network Project Team, and possibly other experts. Subcommittees may be formed to 1) develop and implement data production and analysis standards including spatial and semantic standards for integrating heterogeneous data sets and information; 2) address data submission, management, and analysis issues; 3) develop quality standards and methods for quality control and assurance; and 4) develop common reagents and informatics tools. In these cases, common policies, uniform practices (as needed), and data exchange will be critical to the success of the effort and will enable harmonization and eliminate duplication/overlap.

External Scientific Panel (ESP):

The ESP will provide recommendations to the NIH HEAL Initiative PRECISION Human Pain network Project Team and the PRECISION Human Pain network about the progress and scientific direction of all components of the program. The ESP will be composed of four to six senior scientists who represent broad research community and have relevant expertise, although the membership may be enlarged permanently or on an ad hoc basis as needed. The ESP will meet at least twice a year; some meetings may be conducted by telephone conference. At least once a year, there will be a joint meeting with the Steering Committee for the members of both ESP and Steering Committees to interact directly. Twice a year the ESP will make recommendations regarding progress of the PRECISION Human Pain network and present advice to the NIH HEAL Initiative PRECISION Human Pain network Project Team about changes, if any, that may be necessary in the HEAL Initiative PRECISION Human Pain program.

Dispute Resolution:

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

When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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 submission by the due date, 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 instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

D.P. Mohapatra, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Fax: 301-402-2060
Email: [email protected]

Michael L. Oshinsky, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]

Julia L. Bachman, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-7383
Email: [email protected]

Dana K. Andersen, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 410-868-0638
Email: [email protected]

Inna Belfer, MD, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-435-1573
Email: [email protected]

Xincheng Zheng (Ted), M.D., Ph.D.
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-4953
E-mail: [email protected]

Devon Oskvig, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-5899
Email: [email protected]

Melissa Ghim, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-6570
Email: [email protected]ov

Rachel Altshuler, Ph.D.

National Cancer Institute (NCI)

Telephone: 240-276-5873

Email: [email protected]

Joe Bonner, PhD

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Telephone: 301-827-8303

Email: [email protected]

Mark Egli
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: 301-594-6382
E-mail: [email protected]

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

Elizabeth Gutierrez
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 301-594-8844
Email: [email protected]

Debbie Chen
National Center for Complementary and Integrative Health (NCCIH)
Phone: 301-594-3788
Email: [email protected]

Erik Edgerton
National Institute Of Arthritis And Musculoskeletal And Skin Diseases (NIAMS)
Phone: 301-594-7760
E-mail: [email protected]

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: [email protected]

Sean Hine

National Cancer Institute (NCI)

Telephone: 240-276-6291

Email: [email protected]

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: [email protected]

Judy Fox
National Institute On Alcohol Abuse And Alcoholism (NIAAA)
Phone: (301) 443-4704
E-mail: [email protected]

Section VIII. Other Information

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

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 and 2 CFR Part 200.