Pediatric HIV/AIDS Cohort Study (PHACS) (U19 Clinical Trial Not Allowed) (2024)

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Funding Opportunity Title

Pediatric HIV/AIDS Cohort Study (PHACS) (U19 Clinical Trial Not Allowed)

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

Related Notices

Funding Opportunity Number (FON)

RFA-HD-25-003

Companion Notice of Funding Opportunity

None

Number of Applications

Assistance Listing Number(s)

93.865, 93.279, 93.242, 93.855, 93.121

Notice of Funding Opportunity Purpose

The purpose of this NOFO is to support the Pediatric HIV/AIDS Cohort Study (PHACS) as a transformative and agile program addressingthe developmental and clinical course of persons living with HIV, and perinatally acquired HIV, with an emphasis on youth through reproductive age in the United States.

Key Dates

Posted Date

August 16, 2024

Open Date (Earliest Submission Date)

November 11, 2024

Letter of Intent Due Date(s)

November 5, 2024

All applications are due by 5:00 PM local time of applicant organization.

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

Expiration Date

December 12, 2024

Due Dates for E.O. 12372

Not Applicable

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

Table of Contents

Part 1. Overview Information

Key Dates

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Section II. Award Information

Section III. Eligibility Information

Section IV. Application and Submission Information

Section V. Application Review Information

Section VI. Award Administration Information

Section VII. Agency Contacts

Section VIII. Other Information

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this NOFO is to support the Pediatric HIV/AIDS Cohort Study (PHACS) cohorts as a transformative, streamlined, and agile program addressing the developmental and clinical course of persons living with HIV and perinatally acquired HIV in the United States. The integration of investigators with experience using streamlined scientific and administrative methods and approaches to enhance the function and scientific vision of the cohorts is encouraged.

Background

The goals of this initiative are to support research on the developmental and clinical course of persons living with HIV and perinatally acquired HIV, including the effects of HIV and HIV treatment on fertility, pregnancy and post-partum outcomes, complications, co-morbidities, and co-infections including gynecologic conditions and sexually transmitted infections (STI's) for example syphilis, chlamydia, gonorrhea, HPV, trichom*oniasis and CMV. The transition to adulthood of youth living with vertically acquired HIV who have been on ART for an extended period provides an important opportunity to understand many early developing health issues, including cardiovascular, metabolic, and immune. Early changes in oral health, alcohol, and substance use, behavioral, mental, social, health outcomes may also be evaluated.

The WHO has reported that in 2022 there were approximately 1.2 M pregnant women and 1.5 M children living with HIV. At the end of 2022 there were 9.9K women and 8.8K children accessing ART globally. Individuals with perinatally acquired HIV live with a chronic illness and face the developmental consequences of prolonged HIV, associated co-morbidities, and long-term ART that can affect health, starting with the development of the immune system and over the life course into young adulthood. Of the >1 M people in the US diagnosed with HIV at the end of 2019, 12,355 were among people diagnosed with vertically acquired HIV. The total number of people diagnosed with vertically acquired HIV in the US is disproportionate and occurs among certain racial and ethnic groups with the largest number among Black and Hispanic populations. People with vertically acquired HIV face the developmental consequences of exposure to HIV in utero, long-term antiretroviral therapy (ART) use and associated co-morbidities and co-infections, that affect health throughout life.

There were 2.5 million new cases of syphilis, chlamydia, and gonorrhea reported by the CDC in 2022, with a 555% increase in syphilis reported. These STIs are syndemic with HIV and affect similar populations. Included in the groups most affected by STI's and HIV are pregnant people, those who misuse substances and those aged 13-24.

Thefindings from United States (US) based initiativeshave great relevance internationally since millions of children living with HIV in resource-constrained settings receive treatment and survive into adolescence and adulthood, andmany pregnant people with HIV have access to and use combination antiretroviral therapy to prevent transmission of HIV to their infants andpreserve their own health. The increased availability of antiretrovirals for HIV treatment and prevention has allowed for an increased number of children with perinatally acquired HIV to age into adulthood globally.There is limited clinical data on the long-term impact of HIV and its treatments on this population as they enter reproductive age and have children of their own.

Building on the infrastructure, community connections, and data obtained in the PHACS and similar US cohorts for perinatally acquired HIV individuals, opportunities to study the generational consequences of lifelong ART therapy is critical. For example, the PHACS Adolescent Master Protocol Cohort (AMP Series) includes youth who received very early treatment and may have had nearly lifelong HIV suppression. These data may also inform HIV cure research. Collaborations will continue to be encouraged with other similar cohorts in both resource-rich and resource-constrained settings for data harmonization and sharing.

Cohorts of Interest:

Cohorts of 500 to 1,000 individuals at risk for or living with perinatally or behaviorally acquired HIV, including youth and women of reproductive age are of interest. Recruitment of pregnant and non-pregnant individuals at high risk for or living with HIV (including perinatally acquired) and their children will continue to be encouraged. New enrollments will continue to capture the evolving type and timing of antiretrovirals used as youth transition to adulthood and during pregnancy. The impact of new HIV regimens in these populations will inform the future direction of long-acting antiretrovirals, multipurpose prevention technologies, and vaccines. Activities to support the maintenance and enrichment of the foundational cohorts proposed for study will continue to follow the needed numbers of participants in proposed protocols, but at least 200 new individuals, including children, will be recruited as an addition to the active cohorts each year.

It is expected appropriate control groups, pertinent to the cohorts being studied are included.

Cohorts will also be used in focused Research Pilots (sub-studies) to answer new questions as the research landscape evolves. This will enable the study of priority scientific investigations more rapidly than could be accomplished by individual projects alone.

Scope

The collection of basic information in areas of interest is expected to continue through base protocols and in other supported studies and should include but not be limited to:

• The outcomes and the generational consequences of lifelong ART therapy on:
• Reproductive system pathology and other gynecologic conditions, fertility, sexual maturation, nutrition, growth, endocrine, and bone development
• Cardiovascular, pulmonary, and renal disease risk and complications
• Genomic and metabolomic outcomes of exposure to ART and HIV in reproductive age people
• Correlates of immune system development, breath and HIV control.
• Studies on epigenetic aging on the early development of co-morbidities, and complications.
• Studies on neurodevelopmental, cognitive, and behavioral, outcomes including central nervous system imaging, and peripheral nervous system complications.
• Studies evaluating biomarker correlates of cognitive, cerebrovascular, neuro-inflammatory, neurodegenerative, behavioral and substance exposures use.
• Research on the effects of ART treatment on oral cells/tissues, bone mineral density, and tooth development; mucosal immunity; disease biomarkers; persistence, latency and reservoirs for HIV and pathogens causing oral diseases.
• Studies on the effect of Human Papillomavirus (HPV) vaccine on mucosal immunity and HPV acquisition, clearance, and persistence among those living with HIV.
• Studies on alcohol and drug exposure outcomes in individuals living with perinatally acquired HIV.
• Studies of HIV persistence, latency, reservoirs, and vaccines in reproductive age people
• Research on the effects of HIV and HIV treatment on fertility, pregnancy and post-partum outcomes, complications, co-morbidities, and co-infections including sexually transmitted infections (STI's) (for example syphilis, chlamydia, gonorrhea, HPV, trichom*oniasis and CMV).

Examples of activities supported and encouraged under this NOFO include, but are not limited to:

• Development and implementation of a quality assurance and quality control plan spanning the full data life cycle
• Development of a centralized data storage system for site data.
• Creation and roll-out of a searchable web-based platform to enrich data sharing and broader integration
• Development and utilization of standard, unambiguous terminology for data linkage and integration with multiple data sets, including data dictionaries
• Development of methodologies to support the interoperability of PHACS data with other data sets such as common and metadata standards.
• Establishment of scientific collaborations with investigators.

Essential Features of the U19 Structure

Scientific Administrative Core (SAC) (required)

The Scientific Administrative Core (SAC) provides overall management, communication, coordination, and supervision of the Program.The SAC administers the plan provided in the application to address the short- and long-term management of the Program. The SAC will monitor progress, develop, and implement a project management plan, and define timelines. Additionally, the Scientific Administrative Core will coordinate detailed communication of efforts and progress with NICHD and participating NIH program staff.

The SAC will provide outreach and establish collaborations with other networks and studies, develop and maintain bylaws and policies and mitigate conflicts of interest. In addition, the SAC will convene a Scientific Leadership Group and an Executive Committee, recruit and support the activities of an External Advisory Group (EAG).

The SAC will bring necessary expertise and resources for collaborative protocol development that will ensure feasible and acceptable study design(s), with proven ability to recruit and retain these unique populations through5-15 competitive subcontracts to clinical sites with demonstrated high level prior performance.

The SAC will maintain discretionary funds to support the Emerging Research Pilots (ERPs) and may conduct an annual competition for an Early Career Investigator Award. The SAC will also be responsible for developing plans to mentor new and early-stage investigators to develop independent research careers.

The SAC will also be responsible for holding an annual group meeting to review accomplishments and plan the project agenda.

Data Management and Analysis Core (DMAC) (required)

The Data Management and Analysis Core (DMAC) will be responsible for providing central data storage, data management with safeguards to protect the integrity of the data to all projects within a U19 application and will be responsible for ensuring the submission of data, meta-data and related data analyses to DASH, or other appropriate public databases approved by NICHD. The core will also provide analytic support and development of methods, as needed, to integrate and/or harmonize data and methods for activities across research projects.The DMAC must demonstrate that existing datasets pertinent to the research proposed are usable and accessible through DASH or other publicly accessible data systems.

The DMAC will develop and direct the overarching Project Management Plan for the Cores and Research Projects. The project management plan must include a transition plan to another responsible steward and long-term archival of the data. This is required if the current team no longer manages the data resource, or the entire resource is sunset.

The DMAC will:

• Execute and manage subcontracts for collaborating partners and clinical sites
• Provide support to the Single IRB (sIRB) process and regulatory and compliance management for clinical sites.
• Utilize its relationship with and direct access to clinical sites, personnel, including Clinical Investigators, Study Staff and Community Board (CB) members, to implement all Research Projects and manage and monitor performance efficiently and effectively.
• Serve as the centralized data and resource management entity.
• Provide sample tracking, manage sample storage, oversee laboratory data management and data storage and access.
• Oversee and execute the sharing and transfer of samples and data and the receipt of data for collaborations.
• Provide programming and analytical core services for integrated data analysis.
• Serve as a shared resource to all Cores and Research Projects.

The Core Lead is responsible for ensuring that shared scientific and analytic resources/facilities are available and utilized to the maximum extent possible and that procedures are developed to ensure that such resources are available to members of the research team in a timely manner. The data management and analysis core will also be responsible for ensuring compliance with data sharing policies. The DMAC is encouraged to provide data as it becomes available. To achieve the goal of data sharing from large epidemiologic studies in which data are collected over several discrete time periods or waves, it is reasonable to expect that these data would be released in waves as data become available or main findings from waves of the data are published.

It is expected and encouraged that the DMAC will lead an effort to engage the community to inform the research project, implementation, and dissemination of research findings. This may include translation of findings into resources of interest, coordination of dissemination activities with community members, partner organizations, and relevant service organizations or policymakers.

The effort may also include the support of a community advisory board and/or utilization of a community-based participatory research approach as applicable. Using plain language strategies, dissemination activities should include an effort to translate findings from projects and strategic planning into sustainable community and system-level changes.

The PHACSU19 Research Projects

Each U19 will include a maximum of 3 Research Projects along with Core(s) necessary to support the projects. Research projects should focus onthe effects of antiretroviral treatment (ART) treatment on HIV during reproductive years and/or the developmental and clinical course of persons living with perinatally transmitted HIV. The U19 research program will be facilitated by the sharing of ideas, data, and specialized resources, such as equipment, services, and clinical facilities. The Research Projects proposed must be scientifically meritorious, and complement one another, be synergistic, and support the program's overall theme. Thus, the program's overall scientific merit should be greater than the sum of its parts.

Research Projects require the participation of established investigators in several disciplines or investigators with special expertise in several areas of one discipline. All Senior/Key Personnel (PDs/PIs, Project Leads, Core Leads) must contribute to, and share in, the responsibilities of fulfilling the program objectives.

Each Research Project should contribute materially and intellectually to the specific goals and objectives of the Program Project, contribute expertise and/or resources toward the aims of the Program Project and emphasize collaboration across all components of the U19. Each Research Project should contain the scientific vision which anticipates the ongoing evolution of the field and an emerging scientific agenda by briefly addressing the current state of knowledge on the clinical course of vertically transmitted HIV in children and adolescents, and the critical scientific questions in the clinical course of HIV from preconception to post-partum including the significant scientific gaps and opportunities, and the research, tools, resources and collaborations needed to progress toward filling those gaps to improve health outcomes in these populations.

Research Projects should be supported by the Scientific Administrative Core (SAC),Data Management and Analysis Core (DMAC) and anyother optional appropriate Cores to enhance the research objectives.

The PD/PI must possess recognized scientific and administrative competence, devote a substantial commitment of effort to the program, and exercise leadership in maintaining program quality.

Optional Core (Optional)

Up to 2 optional cores may be proposed to support the research projects proposed for the U19.

Cores are optional and may be included to provide investigators with core resources and/or facilities that are essential for the activities of two or more Research Projects. Core activities must not overlap with each other or with the activities of a Research Project.The Core (optional) will be evaluated as Acceptable or NotAcceptable based on whether it is essential for the proposed research and has the capability to fulfill the proposed function.

Annual Programmatic Meetings

A one- or two-day annual meeting will be held at a location at or near Bethesda, MD or at another NICHD-approved site or may be held virtually as needed. Costs associated with this meeting(s) should be included in the budget.

External Advisory Group (EAG)

An independent external advisory Group (EAG) of investigators who are not current collaborators of the funded programs is expected to be constituted by the PD/PI(s) of the U19 program project and the NIH. The advisory board will meet at least biannually to review the progress in achieving the goals of all research projects participating in the program.The EAG will make recommendations in writing for the continuation or re-direction of any or all projects and activities. Costs associated with the EAG should be included in the budget.

NICHD Data Sharing Expectations and Requirements

The NIH Policy for Data Management and Sharing (Policy) expects researchers maximize the sharing of scientific data and data be accessible as soon as possible and no later than the time of an associated publication or the end of the award period, whichever comes first. NIH requires all applications submitted in response to this NOFO to include a Data Management and Sharing Plan (DMS Plan). The DMS Plan is expected to address the Elements as described in Supplemental Information to the NIH Policy for Data Management and Sharing: Elements of an NIH Data Management and Sharing Plan (NOT-OD-21-014) The DMS Plan will be reviewed and approved by NIH Program Staff prior to award. Awardees will be required to comply with their approved DMS Plan and any approved updates.

For human data, NICHD encourages the use of the Data and Specimen Hub (DASH), a centralized resource for researchers to store and access de-identified data from studies funded by NICHD. Information about DASH may be obtained at https://dash.nichd.nih.gov/. For projects generating large-scale human genetic data, applicants should provide a Provisional or Institutional Certification specifying whether the individual-level data can be shared through an NIH approved repository, such as dbGaP and the Sequence Read Archive, in line with the NIH Genomic Data Sharing Policy.

If use of DASH is not feasible, NICHD expects awardees to share data through other equivalent broad-sharing data repositories. For applications that aim to analyze existing data, DMS Plans should describe where and how other researchers can access that data to enable reproducibility and reuse. Additional information on the Data Management and Sharing Policy is available on the NICHD Office of Data Science and Sharing website.

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

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

Issuing IC, NICHD, and partner components intend to commit an estimated total of $11M to fund 1-2 awards.

Award Budget

Application budgets may not exceed $5.5 M direct costs per year but need to reflect the actual needs of the proposed project.

Award Project Period

5 Years

Section III. Eligibility Information

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
• U.S. Territory or Possession

Other

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

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please referenceNIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applicationsfor additional information.

• 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. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women 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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy StatementSection 1.2- Definitions of Terms.

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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 NOFO. See the administrative office for instructions if planning 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 How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the How to Apply - 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:

Denise Russo, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6871
Email: drusso1@mail.nih.gov

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The application should consist of the following components:

• Overall: required, page limit 12
• Scientific Administrative Core (SAC): required, page limit 12
• Cores: optional, page limit 6, maximum 2
• Data Management and Analysis Core (DMAC): required, page limit 12
• Projects: required, page limit 12, minimum 2, maximum 3

Overall Component

When preparing the application, use Component Type ‘Overall’.

All instructions in the How to Apply - 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.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex.
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP guidance materials.

Project/Performance Site Locations (Overall)

Enter primary site only.

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 NOFO) for the entire application.

TheU19 Program Project PD/PI (s)

• Should be established investigator(s) with demonstrated leadership and administrative capabilities in multidisciplinary research.
• Will be responsible for the projects and cores within the U19 and for communication, collaboration and coordination with other research networks and investigators.
• Will participate and collaborate with the Research Project leads, Core leads and others within the U19 to guide the Program in implementing scientific and administrative decisions.
• Should demonstrate a capacity to ensure participant recruitment based on demonstrated prior site experience and performance.
• Should demonstrate a track record of proactive community engagement in development of research activities.

Budget (Overall)

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

PHS 398 Research Plan (Overall)

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

Research Strategy: Summarize the overall research objectives and strategic plan for the multi-project application. Applications responding to this FOA should describe the central theme of the proposed Program and explain how the proposed Research Projects are synergistic and fit under the overarching Program theme.

• Describe the conceptual wholeness to the overall program project by giving a statement of the general problem area and by laying out a broad strategy for addressing the problems.
• As the strategy develops, cite each research project and core to describe its place in the overall scheme.
• Concisely describe the hypothesis or hypotheses to be tested.
• Highlight the innovation, approach, and significance across the Program Project, including in the research projects.
• Explain ongoing, planned, and potential collaborations nationally to conduct epidemiologic and clinical research.
• Describe the program project's plan and timeline for dissemination of the research data and resources generated. t
• Include an overview of the program project's outreach activities.
• Describe the program project's commitment and plan for developing and mentoring new talent, including new PIs and early stage investigators, toward leadership roles in the cohort and as PIs of R01's.
• Describe prior collaborative arrangements between investigators in the group to explain the development of the current application.
• Describe a Project Management Plan that articulates the strategies and processes that will be used to manage the U19 and achieve the overall goals, including monitoring progress on achievement of Milestones, implementation of the Plan, and proposed Timelines.
• Explain how the proposed program project would enable the stated objectives of the proposed research to be addressed more efficiently and effectively than by a group of individual research project grants.
• Briefly describe the components of the Program Project and how they will interact and synergize to provide a program that is greater than the sum of its parts.
• Explain the strategy for achieving the goals defined for the overall program and how each Core and Research Project relate to that strategy.
• Demonstrate how partnerships between academia and the community have influenced and will continue to facilitate the design and implementation of interventions that leverage new and existing relationships (e.g., academic-based clinical and research sites, and community-based organizations, public health authorities and other private organizations) to optimize the research objectives.

Other Plan(s):

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

• 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.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - 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 How to Apply - 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 How to Apply - Application Guide must be followed.

Delayed Onset Study

Note:Delayed onsetdoes NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form (Overall)

All instructions in the How to Apply- Application Guide must be followed.

Scientific Administrative Core

When preparing your application, use Component Type ‘[Administrative Core]’

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

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

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific 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) (Scientific 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 (Scientific 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.
• The applicant should assemble the necessary multidisciplinary team of established investigators to establish the Scientific Leadership Committee (SLC). Disciplines should be included as required to support the purposes of this initiative.

Budget (Scientific Administrative Core)

Funding for the overall administrative efforts, including secretarial, and/or other administrative services, expenses for publications demonstrating collaborative efforts, and communication expenses should be requested in the budget for this core. Additionally,

• The U19 PD(s)/PI(s) will be expected to provide at least 25% FTE (3 person-months) to the Program and will lead this Core; increased effort is expected if the U19 PD(s)/PI(s) plan to also lead a research project within the U19.
• The U19 PD(s)/PI(s) should provide a discretionary budget to be used for funding of the focused Emerging Research Pilots (sub-studies), for supporting collaboration or co-endorsem*nt agreements with other research networks as indicated, and for accommodating central sub-study-mandated requirements (e.g., specimen shipping costs) on an as-needed basis.
• Funds for one yearly meeting should be included in the budget

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

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

PHS 398 Research Plan (Scientific Administrative Core)

Specific Aims: List in priority order, the broad, long-range objectives, and goals of the Scientific Administrative Core. State the Core’s relationship to the multi-project program goals and how it relates to the Research Projects and any other Cores in the application. Include a brief list of Specific Aims outlining the objectives and functions of the Scientific Administrative Core.

Research Strategy: The overview of the Scientific Administrative Core should articulate the strategy that the Program Project will adopt to achieve the scientific goals and describe the processes/approaches that will be used in decision-making and implementation of activities, including the establishment of scientific priorities, strategies used to manage the Program Project.

• As part of the Core, describe the structure and plans for coordination, administration, fiscal accountability, allocation of funds and other resources, problem identification and resolution, and training.
• Describe the services provided and how the SAC resources will contribute to the objectives of the Research Projects.
• Provide information on how the SAC will provide oversight of the Cores and Research Projects and will promote coordination and collaboration within the program and with investigators and organizations outside the program.
• A plan for determining how the research pilots will be selected should be included.

Letters of Support: Provide letters of support specific to this component.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Scientific 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 How to Apply- 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 Informationform or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - 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 How to Apply- Application Guide must be followed.

Data Management and Analysis Core (DMAC)

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Data Management and Analysis 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 Management and Analysis Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management and Analysis 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 Management and Analysis 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 Management and Analysis Core)

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

Budget (Data Management and Analysis Core)

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

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

PHS 398 Research Plan (Data Management and Analysis Core)

Specific Aims:List in priority order, the broad, long-range objectives, and goals of the proposed Core. In addition, state the Core's relationship to the Program Project and how it relates to the individual Research Projects or other Cores in the application. Include a brief list of Specific Aims outlining the objectives and functions of the Scientific Administrative Core.

Research Strategy: Describe the organizational structure and role of the Data Management and Analysis Core in the overall Program Project research activities and include a strategy for management of data activities that describes internal and external data acquisition strategies to achieve harmonization of systems and procedures for data management, data quality, data analyses, and dissemination for all data and data-related materials. Provide information on innovative capabilities in data analysis and visualization and how these will be developed. Describe the strategies and processes that will be used to manage the DMAC and achieve the overall goals, including monitoring progress on milestones, implementation of the Project Management Plan and proposed Timelines. The DMAC must demonstrate that existing datasets pertinent to the research proposed are usable and accessible through DASH or other publicly accessible data systems.

Describe the utilization of the Core and include the following :

• The Project Management Plan for the Cores and Research Projects.
• A plan for executing and managing subcontracts for collaborating partners.
• Clinical site Single IRB (sIRB) process, regulatory and compliance management.
• DMAC relationship with and direct access to clinical sites, personnel, including Clinical Investigators, Study Staff and Community Board (CB) members, to implement all Research Projects and manage and monitor performance efficiently and effectively.
• The plan for serving as the centralized data and resource management entity.
• How sample tracking, management of sample storage, oversight of laboratory data management and data storage and access will be provided.
• How oversight and execution of the sharing and transfer of samples/data and the receipt of data for collaborations will be managed.
• How programming and analytical core services for integrated data analysis will be provided and how DMAC will serve as a shared resource to all Cores and Research Projects.

Describe how DMAC will demonstrate that existing datasets pertinent to the research proposed are usable and accessible through DASH or other publicly accessible data systems.

Letters of Support: Provide letters of support specific to this component.

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 Data Management and Sharing (DMS) Plan must be provided 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 management and Analysis 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 Project

When preparing your application, use Component Type ‘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.

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

Budget (Research Project)

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

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

PHS 398 Research Plan (Research Project)

Specific Aims:Provide Specific Aims for the Research Project

Research Strategy: Following the instructions in the SF424 (R&R) Application Guide, start each section with the appropriate section heading—Significance, Innovation, Approach.

• Clearly describe the project's objectives and explain its relevance to the overall program's theme.
• As part of the Research Strategy, include information on preliminary studies, data, and/or prior experience pertinent to this application.
• Specify the scientific hypotheses and biomedical significance of the work proposed.
• Describe the Research Project's use of Core services, including why the services are needed and the advantages and cost-effectiveness of Core usage for the Project.
• Provide a timeline and recruitment objectives if pertinent.
• Describe the strategies, techniques and processes that will be used to manage the research project and achieve the overall goals, including monitoring progress with respect to Milestones, and proposed Timelines.

Letters of Support: Provide letters of support specific to the Research Projects.

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 Data Management and Sharing (DMS) Plan must be provided 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 (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

Optional Core

When preparing your application, use Component Type ‘CORE.’

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

Cores are optional and may be included to provide investigators with core resources and/or facilities that are essential for the activities of two or more Research Projects. Core activities must not overlap with each other or with the activities of a Research Project.

SF424 (R&R) Cover Optional 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 (Optional Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Optional 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.

The Core (optional) will be evaluated as Acceptable or "Not Acceptable based on whether it is essential for the proposed research and has the capability to fulfill the proposed function.

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) (Optional 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 (Optional Core)

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

Budget (Optional Core)

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

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

PHS 398 Research Plan (Optional Core)

Specific Aims:

Include a brief list of Specific Aims outlining the objectives and functions of the Core.

Research Strategy:

Provide the following information:

• Objectives: Description of the objectives of the Core.
• Staffing: Brief description of scientific, technical, and support staff.
• Resources: Description of how Core resources will contribute to the objectives of the Research Projects, SAC, DMAC.
• Services provided: Description of current and projected services to other Core and Research Components, as well as the process for prioritizing requests for use of Core facilities by the various Research Projects.
• Management: Description of overall management of the Core, decision-making process for use of Core services, and plans for cost-effectiveness and quality control.
• Utilization of Core: Provide a summary of past and/or projected usage of Core services (e.g., assays performed, etc.). Include estimates of the percentage use of Core unit by the affiliated Research Project components.

Letters of Support: Include letters of support specific to this component.

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 Data Management and Sharing (DMS) Plan must be provided 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 (Optional 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

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply- 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 theNIH Grants Policy StatementSection 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures,2 CFR 200.113 andNIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to theHHS Office of Inspector Grant Self Disclosure Program atgrantdisclosures@oig.hhs.gov.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Significance

Does the program 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 program rigorous? If the aims of the program are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

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

Innovation

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

Approach

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

If the program 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 NOFO:

Is there robust synergy/integration across the programs proposed including the projects and cores?

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 program proposed? Will the program benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria - Overall

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed program 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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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.

Additional Review Considerations - Overall

As applicable for the program 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.

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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For programs 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.

Review Criteria - Scientific Administrative Core

Reviewers will evaluate the following items in determining scientific and technical merit. Reviewers will provide a single impact score for the Science Administrative Core. Reviewers will not give separate scores for the individual items. Reviewers will not provide criteria scores.

• Have the planning and coordination of research activities been adequately described?
• Have the strategies and processes to be used for U19 management to achieve the overall goals, including monitoring progress with respect to Milestones, implementation of the overall Project Management Plan, and proposed Timelines been discussed?
• Are the plans for ongoing communication, and plans for evaluation of the Program Project by internal or external advisory board clearly delineated?
• Are the qualifications, experience, and commitment of the Core director and other Core personnel appropriate?

Review Criteria -Data Management and Analysis Core

Reviewers will evaluate the following items in determining scientific and technical merit. Reviewers will provide a single impact score for the Data Management and Analysis Core. Reviewers will not give separate scores for the individual items. Reviewers will not provide criteria scores.

• Is the plan for services and the process for prioritizing requests for use of Core facilities by the various Research Projects adequately formulated?
• Has information been provided on innovative capabilities in data analysis and visualization, including, GPS and artificial intelligence (AI) strategies to enhance data integration workflows and pipelines, and how these will be developed to serve as community accepted standards?
• Has a description of plans for data harmonization between research projects and cores been provided?
• Has a description of plans for statistical and data management support and for creating and maintaining the necessary clinical infrastructure been provided?
• Is there a description of how DMAC has provided to the public, existing datasets pertinent to the research proposed, that are usable and accessible through DASH or other publicly accessible data systems?
• Are the qualifications, experience, and commitment of the Core director and other Core personnel appropriate?
• Are Core's governance and organizational structure appropriate?
• Has a plan for the development of a centralized information center been described?

Review Criteria - Optional Core

Reviewers will rate the Optional Core as Acceptable or Not Acceptable based on whether it is essential and justified for the proposed research and has the capability to fulfill the proposed function (reviewers will evaluate the number of Projects serviced by the Core; the Core must service two or more Projects).

Reviewers will evaluate the following items in determining scientific and technical merit.

The following items should be considered in providing an overall evaluation of the optional Core(s) as Acceptable or Unacceptable

• Are the cores sufficiently justified?
• Do they support at least two research projects?
• Are the cores adequately connected to the focus of the overall program?
• Are the facilities or services provided by the cores (including procedures, techniques, and quality control) high quality and appropriate?
• Will the services be used effectively?
• Are the core leader(s) and key personnel well qualified and is there an adequate commitment of time?

Review Criteria - Research Projects

Overall Impact - Research Projects

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

Scored Review Criteria - Research Projects

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?

Investigator(s)

Are the Project Leads, 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?

Innovation

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

Approach

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

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 NOFO:Has the research project's use of the Core services, including why they are needed, been adequately explained?

Environment

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

Additional Review Criteria - Cores and Research Projects

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 theGuidelines 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 theGuidelines 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 Animals 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

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations -Cores and Research Projects

As applicable for the program 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

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (e.g.,Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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.

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 NOFO. 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, including the PEDP, as determined by scientific peer review
• Availability of funds.
• Relevance of the proposed project to program priorities.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices.An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access their Summary Statement (written critique) via theeRA 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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

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.

Recipients must comply with any funding restrictions described inSection IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk. For more information on the Notice of Award, please refer to theNIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, seeAward Process.

Prior Approval of Pilot Projects

Recipient-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 recipient institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The recipient institution 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.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by theHHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted inNIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. NIH may terminate awards under certain circ*mstances. See2 CFR Part 200.340 Termination andNIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.

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 (HHS) grant administration regulations at 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 recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The structure of this cooperative agreement encourages interaction and discussion among NIH staff and all involved investigators leading to more robust and innovative research strategies and methods for clinical research to enroll and retain vulnerable reproductive age young adult populations at risk for and living with HIV or at high risk for HIV. Substantive and frequent scientific and administrative involvement of the NICHD and the co-funding ICs (Institutes) Project Scientists will assist the investigators in developing the scientific agenda, refining study protocols, monitoring the progress of the clinical research and participant safety, and coordinating the activities of the Cohorts, including plans for data harmonization, curating, archiving and utilization. The cooperative agreement mechanism will also serve to facilitate cross-Cohort and multi-agency Collaborations, including efforts to ensure participants are prioritized in behavioral and biomedical clinical research.

PD(s)/PI(s) Responsibilities

PD(s)/PI(s) will have the primary responsibility for coordinating the Projects and Cores within the overall Program. Specifically, the PD(s)/PI(s) have primary responsibility as described below.

• The PD(s)/PI(s) will be responsible for defining the research objectives, approaches, and details of the projects within the guidelines of the NOFO and retains primary responsibility for the planning, directing, and executing the proposed scientific activities.
• The PD(s)/PI(s) will monitor all Research Projects and actively promote efforts that foster integration, collaboration, and synergy across the projects.
• The PD(s)/PI(s) will be responsible for ensuring timely compliance with data sharing requirements.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The PD(s)/PI(s) will be responsible for ensuring optimal dissemination of research results by expedient data analysis and key publications within 1 year of study completion and implement explicit data sharing policies for public use thereafter.
• The PD(s)/PI(s) is responsible for the timely presentation/publication of work supported in part or in whole by this Cooperative Agreement. Prior notification to the NICHD regarding any presentations or publications and appropriate acknowledgement of NICHD support are required.

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

The NIH Project Scientists, representing each of the Institutes co-sponsoring the NOFO, will:

• Provide technical assistance, advice, and coordination, and interact with the PD(s)/PI(s) on a regular basis to monitor study progress, regulatory compliance, and quality assurance to ensure the production of high-quality, unbiased results. Monitoring may include: (1) regular communication with the PD(s)/PI(s) and staff, (2) periodic site visits for discussions with recipients' research teams, and (3) observation of activities, quality control, and other relevant matters, as well as (4) attendance at and participation in annual meetings.
• The Project Scientist will work closely with the PD(s)/PI(s) and other Program member scientists to facilitate collaborations and to leverage the resources available to the Program Project.
• Assist PD/PI and SAC in monitoring the progress of ongoing studies, including field data collection, standardization of methods across study sites, and adherence to protocol and quality control measures.
• Assist in data analyses, interpretation, and publication of study results.
• Assist in identifying the need to terminate or curtail the study (or an individual award) in the event of non-participation in the committee/group activities, substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of protocol or substantive protocol changes without prior approval from NIH.
• Collaborate with PD(s)/PI(s) and SAC in overseeing the establishment, maintenance and collaborative scientific efforts of the Program Project and its progress in achieving program goals.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

The duties of the agency Program Official include:

• Carrying out continuous review of all activities to ensure that the objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines.
• Having the option to withhold support to a participating institution if technical performance requirements are not met.
• Performing other duties required for normal program stewardship of grants.

Areas of Joint Responsibility include:

The Project Scientist and the PD(s)/PI(s) will hold regular program-wide discussions to facilitate the achievement of program goals.

The Project Scientist and the PD(s)/PI(s) will collaborate during the course of the award to revise and/or update project milestones as appropriate.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

• When multiple years are involved, recipients will be required to submit theResearch Performance Progress Report (RPPR)annually and financial statements as required in theNIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

• Awardees will provide updates at least annually on implementation of the PEDP.

Section VII. Agency Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)

Finding Help Online:https://www.era.nih.gov/need-help (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:GrantsInfo@nih.gov(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:support@grants.gov

Kathleen Ruth Borgmann
NIDA - NATIONAL INSTITUTE ON DRUG ABUSE
Phone: (301) 594-6561
E-mail: kathleen.borgmann@nih.gov

Anais Stenson, PhD
National Institute of Mental Health (NIMH)
Telephone: 240-926-7572
Email: stensonaf@nih.gov

Hiroko Iida, DDS, MPH
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-594-7404
E-mail: hiroko.iida@nih.gov

Tia Morton, RN, MS
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3073
Email: frazierti@niaid.nih.gov

Pamela G Fleming
NIDA - NATIONAL INSTITUTE ON DRUG ABUSE
Phone: 301-480-1159
E-mail: pfleming@mail.nih.gov

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: rita.sisco@nih.gov

Gabriel Hidalgo, MBA
NIDCR - NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
Phone: 301-827-4630
E-mail: hidalgoge@mail.nih.gov

Section VIII. Other Information