Part 1. Overview Information

Key Dates

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

The Biotypes of Central Nervous System Complications in People with HIV (PWH)

Central Nervous System (CNS) complications, including mild to moderate cognitive impairment and adverse mental health outcomes, are significant comorbidities among individuals living with HIV on antiretroviral therapy (ART). Despite two decades of clinical studies and many clinical trials aimed at improving outcomes related to CNS complications associated with HIV, results have been largely disappointing, with most trials showing minimal or no improvement in neurocognitive function. Researchers are now recognizing that, in addition to inflammation at the cellular level, various patient-level factors such as comorbid conditions (e.g., cardiovascular, metabolic, substance use), concomitant neurological diseases, persistent CNS viral reservoirs, long-term effects of chronic HIV infection, immune system dysfunction, social and structural factors, concomitant drug use and pharmacological treatments including ART-related toxicity can influence CNS pathogenesis and resulting outcomes.

The complexity of these multifactorial pathogenic pathways leads to heterogeneity in outcomes. There has been a shift in psychiatry towards incorporating a neurobiological understanding of CNS disease and patient outcomes rather than solely focusing on clinical phenomenology. To better understand the heterogeneity of CNS outcomes in individuals living with HIV, it is necessary to collect and analyze biological measures related to the etiologies and pathophysiological pathways involved in causing such complications. This effort can help identify biologically distinct disease phenotypes (based on mechanisms), known as biotypes, and allow for the retrospective modeling of disease conditions enabling development of personalized treatment strategies (precision medicine) to mitigate negative CNS outcomes in people living with HIV. The National institute of Mental Health (NIMH) in collaboration with National Institute of Neurological disorders & Stroke (NINDS) and the National Institute of Drug Abuse (NIDA) seeks applications for a Program project to understand the biotypes of CNS complications in people living with HIV as outlined below:

Research Scope and General Structure of This P01 Funding Opportunity

Applications responding to this Notice of Funding Opportunity (NOFO) must include the 3 research projects (listed below) along with an Administrative Core, a Clinical Core and a Data Management Core. Applicants may also propose up to three additional Resource and Analytics Cores; however, these are optional.

Research Projects (Mandatory)

• Data collection, integration, harmonization and analysis of existing data from studies of PWH
• Development, testing, and validation of biologically linked assessments to identify biotypes of CNS complications in PWH
• Machine learning and deep learning-based clustering analysis to identify phenotypic clusters of patients with similar underlying pathophysiology

All proposed components and cores are expected to be integrated and work together as part of a whole project with a singular goal to identify biotypes of CNS outcomes in PWH.

The Program Project is expected to commence with the collection, integration, harmonization, and analysis of existing datasets of NeuroHIV studies from various research sites to identify broad phenotypic clusters of patients with similar underlying pathophysiology (e.g. neurotransmitter imbalance, blood brain barrier dysfunction, neuroendocrine axis disruption, cerebrovascular, inflammatory, comorbidity related, lifestyle, viral reservoir, ART toxicity, metabolic imbalance), with the Data Management Core being responsible for managing this process. Based on these clusters, the team will determine, develop, and test a common set of measures for initial screening (Tier 1) and longitudinal assessments (Tier 2) involving measures and CNS outcomes specified below.

Tier 1 assessments can include common laboratory tests alongside brief biologically linked Research Domain Criteria (RDoC), NIH-Toolbox, and/ or Neuro-Qol-based neuro-behavioral assessments to study constructs relevant to underlying pathobiology and should be of limited duration. Tier 2 assessments will consist of a comprehensive battery of measures, including multimodal assessments of behavioral outcomes, neuronal pathophysiology, virological features, immune dysfunction, co-morbid conditions (e.g., cerebrovascular, metabolic), social and structural factors, concomitant medication use, substance use, and possible ART-related toxicity. The end goal of the research is to employ machine learning and deep learning algorithms to identify the various actionable biotypes of CNS complications among people with HIV using the data obtained from these tiered assessments in combination with existing research data. Datasets selected for identifying the phenotypic clusters should be well-described and appropriate for answering the stated research questions, including appropriate data types and measures. Procedures for selecting datasets that are representative of the population, with the goal of minimizing potential bias, should be described in the application. The three individual research projects must be part of a cohesive whole where the success or failure of each component is tightly linked to that of all the other components.

The datasets that are analyzed and the assessments being developed can include components of all the below-mentioned multifactorial etiologies and pathogenesis pathways that influence CNS outcomes in PWH:

• Demographics, anthropomorphic measurements, socioeconomic status, clinical history including ART medication history, neuro-medical factors including concomitant medication use and the presence of other related comorbidities as well as neurological disorders
• Laboratory data collection and analysis, including CBC, CD4+ T cell enumeration, plasma HIV load, alongside measures of viral dynamics in the CNS (Cerebrospinal Fluid) and periphery, including state of the science assays to quantify viral reservoirs
• Neuropsychiatric assessments using the RDoC framework that can aid in identifying the biological phenotypes of CNS outcomes to evaluate domains of interest, including Negative Valence, Positive Valence, Cognitive systems, Social Processes, Arousal, and Sensorimotor systems
• Assessments of neurological and neuro-behavioral function using NIH Toolbox and/or Neuro-QoL frameworks
• Longitudinal structural, functional, and task-based neuroimaging assessments to comprehend alterations in neuronal circuits, as well as neuroimaging measures of chronic cerebrovascular and BBB dysfunction.
• Collection and analyses of pathway-linked biological measures related to neuro-immune status markers (pro and anti-inflammatory), neurotransmitters and signaling pathways, peripheral immune profiles, neuroendocrine pathways, cerebrovascular dysfunction, immune cell signatures, oxidative stress-related markers, metabolomic markers, drug use-related markers (e.g. endo-cannabinoids, endogenous opioids) and markers related to neuronal health as well as neurodegeneration (e.g., BDNF, Neopterin, NfL, p-tau, GFAP)
• Host and viral genetic/ epigenetic data that can aid in deciphering the biotypes of CNS complications

Further, all the above components must be considered in the context of substance use (nicotine, cocaine, methamphetamine, stimulants, opioids, prescription drugs, and cannabinoids), SUD and substance use data across the lifespan when datasets are analyzed and in developing the assessments.

An Integrated Development Plan (IDP) outlining the activities and tasks for each of the research components, the chronology of the activities, and the linkages between the above-mentioned components must be included in the application. Also, a comprehensive governance plan that delineates how the Team Director, Team leads and if applicable, a Project Manager, will efficiently coordinate and oversee activities across the Research Projects and Cores outlined above should be included in the application.

Applications are expected to include the following items:

Multidisciplinary Team:

Because this effort involves bringing together different modalities of assessments and diverse expertise, applicants must form multidisciplinary teams. It is expected that each team would include individual experts with knowledge and experience in the NeuroHIV field related to:

• Neuropsychiatry, clinical neurology, and neuroimaging
• Substance use disorders and co-morbidities
• Data curation, data science, and machine learning
• Virology and immunology
• Management of multimodal clinical studies

The team can also consist of a panel of 3 or more scientific experts not affiliated with the individual PI institutions that can serve as the Scientific Advisory Panel (SAP) for the project.

Diverse Clinical Sites:

HIV is a global health problem and CNS complications in PWH are prevalent in populations across diverse settings. Consequently, this program project is expected to have diverse clinical sites and data sets obtained from at least one international site and a minimum of three geographically distinct domestic sites (with diverse patient population demographics) across the United States. Using datasets from geographically diverse populations can provide a wider range of demographic, cultural and socioeconomic backgrounds to help capture the true heterogeneity of CNS complications in PWH. These data sets should contain ample cases to enable the identification of phenotypic clusters of CNS complications in people with HIV. Furthermore, a similar configuration of sites should be utilized in the development, testing, and validation of Tier 1 and Tier 2 assessments. All the clinical sites proposed must have access or have the capability to facilitate state of science approaches such as the ability to measure viral dynamics in the CNS, Serum/CNS biomarker quantification and advanced neuroimaging.

Clinical Benefit of Identified Biotypes:

This NOFO supports development, testing and validation of RDoC, NIH-Toolbox, and/or Neuro-Qol-based biologically linked tiered (Tier 1 and Tier 2) assessments that measure CNS outcome linked constructs dimensionally along a spectrum of functioning to identify biotypes of CNS complications in PWH. The Tier 1 and Tier 2 assessments should be developed using iterative design process to meet acceptable standards of reliability, sensitivity, validity, generalizability, accessibility, and engagement across participants. Applications responding to this NOFO should have a strong supporting rationale for the approach they use to develop the Tier 1 and Tier 2 assessments and how the assessments represent a significant improvement over the current state of the science. Further, the applicants are expected to demonstrate, the readouts of the Tier 1 and Tier 2 assessments can provide insights for conceptualizing personalized treatment strategies to alleviate CNS complications in PWH.

Milestones:

Annual Go/No-Go milestones must be proposed in the overall Integrated Development Plan to reflect progress on each of the above-mentioned research components. Applicants should clearly outline how the research components are interrelated and the order in which each research component needs to be successfully completed before initiation of other components. A discussion of the milestones relative to the progress of specific research components and the implications of successful completion of the milestones for the other research components should be included. Milestones should be well-described, quantifiable, and scientifically justified to allow program staff to assess progress. Specific aims or a list of activities are not considered milestones because they would not enable evaluations of specific goals.

The clarity and completeness of the outlined milestones regarding specific goals and feasibility are critical. Milestones should provide clear indicators of continued success or emergent difficulties. Evaluation of the proposed milestones will be a criterion of the scientific peer review.

Annual Meeting :

An annual meeting is required and can be held in person or virtually with the following in attendance: Principal Investigators, NIH Program Staff, Scientific Advisory Board/ Committee (if constituted), Research Project Leads, Scientific Core Leads and Co-Investigators. During this meeting, presentations will be expected to include summaries of all goals, timelines proposed and milestones achieved along with Go/No-Go decisions, and a description of all problems that may be encountered and that may have an impact on the future direction of the project. The objective of the meeting is to ensure that NIH understands the advances in the program, to provide an opportunity for collective problem-solving among investigators, and to reinforce the programmatic goal of maintaining an integrated scientific approach to identifying Biotypes of CNS outcomes in PWH.

Cores

In addition to the three mandatory research projects, the research application is expected to include an Administrative Core, Clinical Core, and a Data Management core. Up to 3 additional Research and Analytic optional cores can be included in the application.

Administrative Core (Required): Each application must contain an Administrative Core that is responsible for the overall management, communication, coordination, and oversight of the program administered by a consortium of identified experts

Clinical Core (Required): Each application must contain a Clinical Core as one of the components that will be involved in developing, testing, and validating Tier 1 and Tier 2 assessments to identify biotypes of CNS complications in PWH. The clinical Core must be composed of a multidisciplinary team of investigators and have representatives from all the clinical sites where the Tier 1 and Tier 2 assessments are being conducted. The clinical core may include a Scientific Advisory Committee consisting of experts to provide overall direction and guidance to develop, test and validate biologically linked (RDoC, NIH-Toolbox, and Neuro-Qol-based) Tier 1 and Tier 2 assessments.

Data Management Core (Required): Each application must contain a Data Management Core as one of the components that will provide reliable data management, data analysis and communication among the proposed P01 research sites, as well as a reasonable plan to develop a data science framework for facilitating the workflow for data aggregation and analysis between the proposed research components. The data management team should include appropriate data science staff with expertise in advanced machine learning and software engineering support. The Data Management Core may include a Scientific Advisory Committee consisting of experts to provide overall direction and guidance related to data science approaches to identify biotypes of CNS complications in PWH. The Data Management Core should provide details on plans to identify best practices, standards, tools, workflows, and computational infrastructures, and to reuse those already in use by the research community, where applicable.

Resource and Analytic Core (Optional): Applicants may propose up to three Resource and Analytic cores (e.g., Biomarker Core, Neuroimaging Core, Comorbidities Core) to provide guidance, analytics support, and resources necessary for accomplishing the goals of the three individual research components. Each of these cores, when proposed, can include a Scientific Advisory Committee consisting of experts to provide overall direction and guidance in specific areas of expertise essential for achieving the proposed goals of the grant. A Resource and Analytic Core must not duplicate resources already available at the institution(s). While the addition of the Resource and Analytic Core(s) is optional, if included in the application, the core(s) should be critical to the success of the P01 project.

Non-Responsive Applications

The following applications will be considered non-responsive to this NOFO and withdrawn from consideration without review:

• Applications that propose intervention development, efficacy, or effectiveness studies for the treatment of HIV-associated CNS complications
• Applications lacking milestones, multidisciplinary teams, and diverse clinical sites (At least, one international and 3 geographically distinct clinical sites)
• Applications lacking preliminary data, and annual Go-No Go milestones in the IDP.
• Applications lacking detailed plans for any of the research components
  

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

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

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

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

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

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. 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 SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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 Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Email: [email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

All Program project applications must include the components listed below:

The application should consist of the following components:

• Overall: Required: (1)
• Administrative Core: Required (1)
• Clinical Core: Required (1)
• Data Management Core: Required(1)
• Resource and Analytic Core: Optional (0-3)
• Research Projects: Required (3)

Overall Component

When preparing the application, use Component Type Overall .

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

Enter primary site only.

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

Research and Related Senior/Key Person Profile (Overall)

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

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

Budget (Overall)

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

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

PHS 398 Research Plan (Overall)

Specific Aims:

Describe the central scientific, data and resource collection/production goals of the proposed P01 program project application, and aims in order of priority. List the titles of all 3 Research Projects and Cores. Outline how the Research Projects and Cores will synergetically contribute to attaining the aims of the proposed P01 program project as well as the overall goals of the Biotypes of Central Nervous System Complications in People with HIV initiative.

Research Strategy: The Research Strategy must include all of the following.

• Provide a chart to describe the overall organizational structure of the proposed P01 project with an overview of the performance sites and responsibilities of the Research Projects and Cores Define the roles among the different entities.
• Summarize the expertise of the multidisciplinary team to highlight adequate expertise in the below noted categories needed to accomplish the research and goals of the proposed P01 project.
  • Neuropsychiatry, clinical neurology and neuroimaging
  • Substance use disorders and co-morbiditie
  • Data curation, data science and machine learning
  • Virology and immunology
  • Management of multimodal clinical studies
• Outline the rationale and brief research approach/plan for individual research projects and core facilities proposed. Summarize how the individual research components and cores can synergize to accomplish the individual and overall goals of the proposed program, in the context of understanding the Biotypes of CNS complications in PWH
• Explain how the proposed Research Projects and Cores will contribute uniquely to the overall research aims of the P01 projectand the overarching goals of the Biotypes of Central Nervous System Complications in People with HIV initiative, including the feasibility to design personalized treatment strategies that address specific biological mechanisms related to the biotypes.
• Describe approaches to ensure participation of diverse populations in the study.
• An Integrated Development Plan outlining the activities and tasks for each of the research components, the chronology of the activities, and the linkages between the above-mentioned components must be included in the application.
• Annual Go/No-Go milestones must be proposed in the overall Integrated Development Plan to reflect progress on each of the research components.
• Describe the appropriateness of selecting the study population to accomplish the goals of the project, including controls for comparison.
• Provide an overview of project workflow incorporating quality control/quality assurance measures and decision-making process (Workflow and experimental designs should ensure robust and unbiased results, which are essential for the utility of data generated through this project).
• Identify possible rate-limiting steps as it relates to overall workflow across different research components of the program project, and include plans to address possible bottlenecks, as appropriate.
• Include a descriptive and graphic timeline for the overall proposed workflow including yearly milestones.
• Provide alternative strategies, as appropriate, should any research projects or core fail to perform as expected.

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

• Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants. Letters of support for the overall should be included with the Overall component. Letters of support for individual Research Projects or Cores should be included with those components of the application. Letters of support should indicate the specific activities the individual or organization will perform in pursuit of the project goals. Letters of support from individuals or organizations without a specific role in the project should not be included.
• If an application plans to utilize the infrastructure or resources of existing projects, whether funded by NIH, other governmental or non-governmental entities, letters of support detailing the terms of collaboration and data sharing must be included.
• For procurement and utilization of data, biological samples and specimens in the P01 project, letters of support or approval for use of those samples and specimens should be included

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

Other Plan(s):

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.

All instructions in the SF424 (R&R) 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.

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this Notice of Funding Opportunity (NOFO) are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100). Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. . NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this NOFO are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission. The NDA website provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this NOFO prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied. For more guidance on submitting data to NDA, refer to the NDA: Submitting and Sharing Data NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application, use Component Type Administrative Core.

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

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

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

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

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

List all performance sites that apply to the specific component.

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

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

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

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

Budget (Administrative Core)

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

The P01 overall PD/PI(s) is/are expected to serve as a Project Lead of the Administrative Core with a minimum effort of 0.6 person months towards the admin core. If multiple PD/PIs serve as co-leads for the Administrative Core, each of them are expected to devote at least 0.6 person months.

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

PHS 398 Research Plan (Administrative Core)

Specific Aims: The application must outline the objectives of the Administrative Core to address issues of coordination, communication, and management, indicating how the Core will contribute to the project’s goals, as well as to the overarching goal of the Biotypes of CNS complications in PWH initiative.

Research Strategy:

• Describe a staffing and administrative plan that includes a discussion of the structure and roles of administrative and scientific staff for the Administrative Core, including individual responsibilities, the functions to be performed, and how resources will be prioritized, allocated, and managed. The description should clearly indicate the facilities, resources, services and professional skills that the Administrative Core will provide.
• Describe the Administrative Core's role in managing all aspects of the production of datasets, tools, analyses, and data management of the proposed P01 project.
• Describe how each Research Project and Core will draw upon the Administrative Core and how it, in turn, will respond to Research Project or Core needs.
• Describe how the Administrative Core will ensure that all Research Projects and Cores are meeting the performance objectives and milestones, as well as any novel features of the Administrative Core that enhance the collaborative effort, including optimizing communication, decision-making and resource sharing among the Research Projects and Cores.
• Describe how the Administrative Core will support the development and implementation of standard operating procedures (SOPs); maintain fidelity to research procedures and fiscal accountability; ensure quality control (QC) for data and/or tool generation; ensure timely data sharing; oversee the analyses of all data by the Data Core; and oversee the overall coordination of the Biotypes of CNS complications in people with HIV initiative.

Additional Information Required in the Administrative Core Research Strategy:

Governance Plan: The application must outline a detailed governance plan describing how the Team Director and a Project Manager (if proposed) will organize and direct efforts across the Research Projects and Cores. When multiple institutional sites are involved, a detailed description of the cooperative administrative arrangements should be included. Documentation of these arrangements should be included in the Overall Letters of Support section.

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

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

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Administrative Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Clinical Core

When preparing your application, use Component Type Clinical Core.'

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

SF424 (R&R) Cover (Clinical 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 (Clinical Core)

Enter Human Embryonic Stem Cells in each relevant component.

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

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

In the biosketches, outline the experience of personnel required to manage the activities of the Clinical Core.

Budget (Clinical Core)

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

The Clinical Core Lead(s) must commit to a minimum of 0.6 person months of effort towards the clinical core.

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

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

PHS 398 Research Plan (Clinical Core)

Specific Aims: State in priority order the aims of the Clinical Core, indicating how this core will contribute to the proposed goals of the P01 program project, as well as to the overarching goal of the Biotypes of CNS complications in PWH initiative.

Research Strategy:

• Describe a staffing and operation plan that includes a discussion of the structure, roles and responsibilities of scientific and technical staff for the Clinical Core, including the functions to be performed and how resources will be prioritized, allocated, and managed. The description should clearly indicate the facilities, resources, services and professional skills that the Clinical Core will provide for the Research Projects and Resource Cores. The clinical Core must be composed of a multidisciplinary team of investigators and have representatives from all the clinical sites where the Tier 1 and Tier 2 assessments are being conducted.
• Describe the capability each of the clinical sites to facilitate state of science approaches such as the ability to measure viral dynamics in the CNS, Serum/CNS biomarker quantification and advanced neuroimaging
• Outline the rationale and research approach/plan for developing Tier 1 and Tier 2 assessments in the proposed Clinical Core.
• Describe prior experience and/or plans for patient recruitment. Describe plans for patient screening and recruitment along with a proposed timeline for the assessments and acquisition of biospecimens.
• Describe plans for developing consent forms for broad data sharing without any identifying subject information.
• Provide details on data collection (clinical, phenotypic and associated metadata) using acceptable data collection standards.
• Provide adequate justification to ensure novel methodologies and assessment tools being developed are transformative and can conceptually provide new insights to the NeuroHIV field
• Describe plans for developing and implementing standardized and uniform approaches and quality control measures. Highlight any innovative aspects of the proposed protocols, procedures, and/or tools for the procurement.Include evidence for feasibility, including any supporting general and background preliminary findings.

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

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

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

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

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

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

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

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Clinical Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Data Management Core

When preparing your application, use Component Type Data Management Core.

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

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

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management 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 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 Core)

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

Budget (Data Management Core)

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

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

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

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

PHS 398 Research Plan (Data Management Core)

Specific Aims: State in priority order the aims of the proposed Data Management Core, indicating how the core will contribute to the proposed goals of the P01 Project as well as to the overarching goals of the Biotypes of CNS complications in PWH.

Research Strategy: Explain how the Data Management Core will serve the proposed P01 project. Provide an overview as well as a detailed plan on data management and analysis practices.

• Describe database infrastructure and plans for information management and monitoring, management of complex multimodality data, statistical analysis and inference of biological mechanisms, data integration and registration to common tissue and cell coordinate systems, and computational modeling if appropriate.
• Propose data analysis methods and procedures for successful implementation of the project goals including details of machine learning analysis algorithms and data hierarchy.
• Describe how the data core will provide data science expertise, data integration and analysis support, and study design and statistical support/services to project investigators.
• Provide statistical rationale about data quality and informatics analysis.
• Describe and offer evidence for the feasibility of the proposed data management plan, the advantages of any new data management methodologies, the potential pitfalls and alternative approaches for data management, and how these might impact the overall progress of the P01'S research objectives and the goals of the network.
• Propose and justify data/metadata standards and formats to be used while demonstrating flexibility for adopting different ones.
• Describe plans for maintaining records for clinical data, biospecimen procurement and associated metadata elements in close collaboration with the Clinical Core.

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

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

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Data Management Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Resource and Analytic Core

When preparing your application, use Component Type Resource and Analytic Core.

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

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

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Resource and Analytic Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Resource and Analytic Core)

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

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

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

Project /Performance Site Location(s) (Resource and Analytic 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 (Resource and Analytic Core)

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

Budget (Resource and Analytic Core)

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

Resource and Analytic Core Lead(s) must commit to a minimum of 0.6 person months of effort towards the Resource and Analytic cores.

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

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

PHS 398 Research Plan (Resource and Analytic Core)

Specific Aims: State in priority order the aims of the proposed Resource and Analytic Core, indicating how the core will contribute to one or more of the Research Projects and Cores of the P01 project. Provide a concise description of the broad activities and services of the proposed Core. Indicate why the Resource Core is an essential part of the proposed project, and how the proposed services will facilitate accomplishment of the proposed goals of the Biotypes of CNS complications in PWH

Research Strategy: Explain how the Resource and Analytic Core will contribute to the research activities for one or more Research Projects and Cores of the P01 project. Note: Resource and Analytic Cores should not duplicate resources already available at the institution. Also, the activities of Resource and Analytic Cores must not overlap with each other or with the activities of a Research Project(s) and/or of other Cores.

• Describe the facilities, services and/or types of resources that will be provided and managed, and how they will meet the specific needs of each Research Project and/or Core. Include a prioritization plan for providing the services and/or resources, and plans for quality control.
• State the rationale for centralizing activities in a Resource Core rather than including them in individual Research Projects.
• If one of the Core’s objectives is to improve technologies, tools, and or reagents, describe limitations and gaps of the current technologies and tools in throughput, sensitivity, selectivity, scalability, spatiotemporal resolution and reproducibility. Propose improvements that will address the current limitations and gaps, and how said improvements, if achieved, will enhance the goals of the project as well as the overarching goals of the network.
• Describe the unique and innovative contributions that will be made by this Resource Core.
• Describe the advantages of any new resource types and methodologies, the potential pitfalls and alternative approaches, and how these might impact the overall progress of the P01's research goals.
• Describe the role(s) of the Resource Core Lead and key participants without duplicating information provided in the Biosketches or the Budget Justification.
• If the Resource Core is at a different geographic location than the Research Projects and Cores it serves, describe plans for data/material(s) transfer and communication.
• Describe any plans for collaborations or contracting for specific services to outside facilities (academia and/or industry), with justification. Corresponding letters of support/service should be included in the Letters of Support section below.

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

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

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

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

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

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

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

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Resource and Analytic Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Research Projects

When preparing your application, use Component Type Research Projects.

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

SF424 (R&R) Cover (Research Projects)

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 Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

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

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

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

Facilities and Other Resources:

In this section, describe the institutional, commercial, and industrial investments and resources that constitute the environment for this research program. New cost-sharing commitments are not required. Some examples of institutional environment could include recruitment and salary support of new faculty or professional staff positions to support the resource components, startup packages, space renovations for team investigators, new facilities within the research and core components, dedicated equipment for research and resource components, dedicated budget lines or facilities for a team consortium, dedicated use of commercial products and technologies, equipment and technology contributions from commercial collaborators, etc. Summarize how the facilities and resources under each component are complimentary and critical to the overall research goals and plan for this P01 application. Facilities and resources specific for individual Research Projects and Cores should be detailed under the respective component sections.

• In addition to standard items, describe existing facilities and/or other resources (such as existing institutional shared resource cores) available to the proposed P01 program.
• As applicable and pertinent to the proposed research, describe partnerships (e.g., with industrial entities) that will provide relevant capabilities.

Equipment:

Summarize the availability and accessibility of all necessary equipment for the proposed P01 program, and how they are complimentary and critical to the overall research goals and plan of this application. Equipment specific for individual Research Projects and Cores should be detailed under the respective research project and core sections.

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

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 Projects)

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

Budget (Research Projects)

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

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

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

PHS 398 Research Plan (Research Projects)

Specific Aims: State in priority order the aims of the proposed Research Projects, indicating how the project will contribute to the Project's objectives as well as to the overarching goal of the Biotypes of CNS complications in PWH initiative. Provide a concise description of the rationale for the specific aims and questions proposed, and the overall approach to address the goals of the research project.

Research Strategy:

1. Significance

• Describe the overall objective(s) and the impact of the proposed research project towards the overall goals of the P01 progam as well as the overarching goals and expected outcomes of the Biotypes of CNS complications in PWH initiative.
• Explain the contribution(s) of each Research Project to the overall goals of the P01 and how it will interact with and benefit from other Research Projects and Cores.
• Provide the rationale for the specific goals of the Research Project, in relation to the overall goals of the P01 program.
• Provide a clear outline of the preliminary data supporting the rationale for the proposed research project.
• Describe the overall strengths, weaknesses, and rigor of the preliminary data, including the data in published studies that are used to support the rationale for the proposed studies.
• Address potential shortcomings of the research plans, and strategies for dealing with them.
• Describe the unique contribution of experts in the multidisciplinary team to the goals of this Research Project.

2. Innovation

• Describe the unique and innovative contributions that will be made by this research project with regard to questions, tools, and approaches to generate novel insights on Biotypes of CNS complications in PWH.

3. Approach

• Define comprehensiveness or breadth and depth for collection and analysis of data the proposed project.
• Address how the proposed experimental design will ensure that the data generated are rich in content and can be easily used by the broader NeuroHIV research community.
• Describe production workflow including throughput as well as rate-limiting steps. Provide plans for assessing and improving this pipeline, where applicable.
• Describe scalable methods with preliminary data and case studies to support the feasibility of collecting and analysis high-quality data in a cost-effective manner.
• Provide current estimates of data quality and plans for how data quality will be evaluated during the course of the project. Describe quality control/quality assurance measures and decision-making processes.
• Provide a plan to ensure appropriate standardization of assessments, assays, samples, data, and controls that will be used for this research project. Propose plans to coordinate with other research components and cores on these aspects.
• Describe and offer evidence for the feasibility of the proposed approaches, the advantages of any new methodologies, assays, outcome measures, analytical/statistical models, and the potential pitfalls and alternative approaches for the research project. Also, describe how these might impact overall progress of the research project and goals of the proposed project.
• Discuss plans (if any) for collaborations with outside resources (academic facilities, contractors and/or industry), other than the Resource Cores in this application.

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

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

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

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

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

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

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

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

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Research Projects)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

Foreign Institutions

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

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH 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 the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential 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.

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 SF424 (R&R) Application Guide.

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.

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.

NIMH expects investigators for this funding announcement to collect Common Data Elements (CDEs) for mental health human subjects research. Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications involving human research participants. The necessary funds for collecting and submitting these CDE data from all research participants to the NIMH Data Archive (NDA) should be included in the requested budget. A cost estimator (https://nda.nih.gov/ndarpublicweb/Documents/NDA_Data_Submission_Costs.xlsx) is available to facilitate the calculation of these costs. NIMH may seek further information regarding CDEs prior to award. Additional information about CDEs can be found at the NIMH webpage on Data Management and Sharing for Applicants and Awardees.

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 the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

The synergy between the 3 research components of the program project should demonstrate/reflect the ability to achieve the goals of the Biotypes of CNS complications in PWH initiative. Evaluate if the proposed number and composition of Research Projects and Cores can effectively attain the objectives of the Biotypes of CNS complications in PWH program project. The entire research application will receive one Overall Impact Score based on critical consideration of all the components of the entire application.

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

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

Significance

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

Specific to this NOFO:

• To what extent do the proposed aims and scientific questions align well with the overarching goals and the expected outcomes of the Biotypes of CNS complications in PWH initiative?
• How likely are the expected results anticipated to yield substantial data related to the comprehensive discovery and characterization of actionable CNS biotypes that can help better comprehend the heterogeneity of CNS outcomes in PWH?
• Evaluate to what extent do the successful completion of the aims lead to transformative advances in the field, including but not limited to offering insights for design personalized treatment strategies that address specific biological mechanisms related to the biotypes?

Investigator(s)

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

Specific to this NOFO:

• To what extent does the team exhibit diverse, collaborative and multidisciplinary expertise, such that it consists of appropriate content experts recognized as leaders in their field?
• Evaluate if the team includes adequate expertise in:
  • Neuropsychiatry, clinical neurology and neuroimaging
  • Substance use disorders and co-morbiditie
  • Data curation, data science and machine learning
  • Virology and immunology
  • Management of multimodal clinical studies
• Evaluate if the proposed PD(s)/PI(s) have demonstrated sufficient ability to organize, direct, and administer a complex research project?
• Assess the appropriateness of the knowledge, experience and leadership abilities of the individual Research Project and/or Core leads Evaluate the track record of previous collaborative teamwork endeavors of the project team in terms of achieving desired outcomes.
• Is there sufficient evidence that the research team has been/will be able to work together effectively to accomplish the research proposed in the projects?
• Evaluate the adequacy of the leadership to manage day-to-day project management activities?

Innovation

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

Specific to this NOFO:

• To what extent does the application demonstrate sufficient evidence to ensure novel methodologies and assessment tools being developed are transformative and can conceptually provide new insights to the NeuroHIV field?
• Evaluate the impact of the novel methodologies and/or assessment tools generated by this application on driving transformative, paradigm-shifting advancements in the field.

Approach

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

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:

• Evaluate the rigor of the approach to ensure that high quality clinical data will be generated.
• To what extent does the application adequately describe and discuss experimental designs to ensure the data quality and comprehensiveness?
• Evaluate if the application provides sufficient evidence of how the individual research component goals are set and can be attained?
• Evaluate if the synergy between individual research components and cores are adequate to accomplish the individual and overall goals of the proposed program, in the context of understanding the Biotypes of CNS complications in PWH?
• Evaluate if the timeline suggested is reasonable for the work proposed and assess the feasibility?
• Assess the effectiveness of identifying the rate-limiting steps and whether they are appropriately addressed?
• Evaluate the adequacy of the data quality, validity and accessibility characteristics?

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?

Overall Coordination

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

Milestones

Are proposed milestones clear and quantitative? Do the milestones establish feasibility for all aspects of the proposed research? Does the application include plans for critically evaluating and revising milestones on a regular basis? Are there additional key research components that need to have separate milestones specified?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Not Applicable

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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.

2. Review and Selection Process

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

As part of the scientific peer review, all applications will receive a written critique.

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

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

Applications will be assigned 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 Mental Health Council. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690)) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

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

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

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

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

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

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

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the 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 the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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

Finding Help Online: 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: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

Vasudev R. Rao, MBBS, MS.
National Institute of Mental Health (NIMH)
Telephone: 301-825-3259
Email: [email protected]

Vasundhara Varthakavi
NIDA - NATIONAL INSTITUTE ON DRUG ABUSE
Phone: 240-669-5020
E-mail: [email protected]

William Patrick Daley
NINDS - NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Phone: 3014961431
E-mail: [email protected]

Nicholas Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: [email protected]

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: [email protected]

Pamela G Fleming
NIDA - NATIONAL INSTITUTE ON DRUG ABUSE
Phone: 301-480-1159
E-mail: [email protected]

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

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.