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

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

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

This funding opportunity announcement (FOA) is being re-issued with the aim of supporting the continuation of the NNTC as resource for studies on the neuropathogenesis of HIV-1 induced CNS and PNS dysfunction in the context of ART and research towards a cure of HIV-1 infection from the CNS including studies of viral persistence, latency, reactivation and eradication.

The NNTC is currently comprised of four NNTC Clinical Sites and one Data Coordinating Center (DCC). The consortium works cooperatively to provide NeuroAIDS investigators with clinically annotated data sets and with specimens that have been obtained during life (plasma, CSF, blood); and at post-mortem (HIV-1 positive brains, HIV-1 negative brains, PNS tissue, heart, lung, liver, kidney, lymph nodes, blood and cerebral spinal fluid (CSF)). The NNTC Clinical Sites recruit and manage the NNTC Cohort which is comprised of late stage HIV-1 positive subjects who are willing to participate in organ donation and most of whom use ART. The NNTC Clinical Sites perform comprehensive clinical assessments (neuromedical, neuropsychological, psychiatric and virological data are collected ante mortem), and then at post mortem, they collect brain and neurological tissues and fluids, perform neuropathological diagnosis and laboratory assessments and transfer all data generated from these activities to the data repository which is maintained by the DCC. Research investigators may query the available NNTC clinical specimens and data at the NNTC website.

HIV-1 induced neurological dysfunction and HIV-1 persistence in the CNS continue in people with chronic HIV-1 infection despite suppressive ART. To provide NeuroAIDS investigators with resources from people who are surviving chronic HIV-1 disease with ART, the resources of the CNS HIV-1 Antiretroviral Therapy Effects Research (CHARTER) studies are now fully integrated with the NNTC. The CHARTER specimens (plasma, CSF, buccal swabs, nucleic acids and neuroimaging) are maintained by one of the four NNTC Clinical Sites, the California NeuroAIDS Tissue Network. CHARTER data sets (clinical, laboratory, genetic, neuroimaging and research) are maintained by the DCC, and external requests for data or tissues are managed by the DCC in collaboration with the NNTC Clinical Sites. In affiliation with the DCC, the Global HIV-1 CSF Escape Consortium has also recently been established. CSF escape is a rare phenomenon that occurs when rebound viremia is detectable in the CSF of patients despite ART suppression of the virus in the peripheral blood. Researchers may contribute their relevant data to the DCC for potential collaborative studies and participate in on-line forums by contacting the DCC. The specimens from CSF escape cases are stored at the clinical sites of origin. This funding opportunity encourages expansion of the existing multi-site brain bank structure of the NNTC to affiliate the DCC with other national and international clinical sites that have collected CNS and PNS specimens and clinical/experimental data. The DCC-affiliated Clinical Sites will contribute NeuroAIDS data sets. The DCC will manage external requests for the data and the specimens stored at the affiliated clinical sites or other appropriate location. This will ensure that NeuroAIDS investigators have access to CNS and PNS resources that are difficult to obtain from HIV-1 infected individuals across the lifespan.

The NNTC has defined criteria for a unique subset of HIV-1 positive participants of the NNTC Cohort who were on suppressive ART in life and who participated in organ donation. Brain and other tissue specimens from this unique subset of the NNTC repository are entitled, "Virally Suppressed Cases" (NOT-MH-16-008). ART suppresses HIV-1 RNA levels in peripheral blood and CSF, yet it does not completely eliminate the virus. Viral rebound becomes detectable in the peripheral blood and CSF within weeks when patients cease taking their anti-retroviral medication. The NNTC successfully documents the neurocognitive status and last known HIV-1 viral load prior to death for the late-stage NNTC Cohort. However, ethical and palliative care of individuals often involves cessation of ART. Brain and fluid samples obtained in combination with de-identified medical records from donors who die suddenly from other causes may support neuropathological studies on the mechanisms by which comorbidities develop in association with neurological complications of chronic HIV-1 disease. Additional brain specimens and clinical data from HIV-1 positive donors who die suddenly from other causes are also needed to support researchers involved in determining the cellular and tissue sources of latent HIV-1 under suppressive therapy. This is critical since latent virus may be a source of rebound viremia if ART resistance develops in the CNS or upon cessation of therapy. This FOA encourages identification of additional CNS and PNS research resources from individuals who are surviving HIV-1 infection with ART suppression, yet die suddenly from other causes.

The key consortium wide objectives for this and the companion FOA, RFA-MH-18-251, are to ensure that NNTC CNS and PNS tissues/fluids and data are available and useful to investigators for examining emerging topics in the NeuroAIDS field such as research: a) towards a cure of HIV-1 infection from the CNS including studies of viral persistence, latency, reactivation and eradication in the context of ART; b) on neuropathogenic mechanisms of HIV-1 induced neurological dysfunction in the setting of ART; and c) on understanding comorbidities associated with HIV-1 induced neurological dysfunction including aging with chronic HIV-1 disease. Through these two FOAs, the NIH expects to continue to fund up to four NNTC Clinical Sites (RFA-MH-18-250) and one Data Coordinating Center (RFA-MH-18-251).

The key objective for this FOA is to pursue the continued operations of the NNTC Clinical Sites. The NNTC Clinical Sites are responsible for the following activities of the consortium: 1) recruitment, clinical assessment and follow-up of the late-stage NNTC Cohort; 2) collection and maintenance of ante mortem and post mortem specimens along with neuropathological and laboratory analysis of specimens; 3) collection, de-identification and quality control assessment of data sets; 4) rapid transfer of all data sets affiliated with the NNTC Clinical Sites to the DCC including clinical, laboratory and inclusion of a specimen inventory of all tissue and fluid specimens collected and housed at the clinical sites; 5) distribution of CNS and PNS tissue and fluid resources to approved NeuroAIDS investigators; and 6) effective collaboration with the DCC, and other clinical sites affiliated with the NNTC, to provide CNS and PNS specimen and data resources to approved investigators engaged in NeuroAIDS research.

This FOA encourages the use of the following common, standardized approaches for the NNTC Clinical Site activities: clinical assessment measures, protocols and a database system to rapidly exchange high quality data sets with the DCC. Such a standardized, high quality repository of NeuroAIDS specimens and data will enable multidisciplinary query capabilities and tools to accelerate discovery research on the neuropathogenesis of HIV-1 induced CNS and PNS dysfunction in the context of ART, and CNS-based HIV-1 cure research.

Recruitment strategies used to selectively enhance the recruitment of HIV-1 infected subjects into the NNTC Clinical Site cohort should be responsive to the evolving research needs of investigators for CNS and PNS tissue, fluids and data sets. The needs of NeuroAIDS investigators for research resources may be identified and informed by the scope of prior requests for NNTC resources, statistical and epidemiological analysis of the NNTC database by the DCC and the state of the science. This FOA encourages development of recruitment strategies to enhance the NNTC Cohort to help address the following research areas of high priority to the NIH: a) curing HIV-1 infection in the CNS, including studies of viral persistence, latency, reactivation and eradication in the context of ART; b) understanding neuropathogenesis of HIV-1 induced CNS and PNS dysfunction in the context of ART; and c) understanding comorbidities associated with HIV-1 induced neurological dysfunction including aging with chronic HIV-1 disease.

Protections for Human Subjects: Applications with data collection plans that involve multiple respondent groups (e.g., clients/patients, therapists/providers, supervisors, administrators) should address provisions for human subject protections and consenting procedures for all participant groups, accordingly. Clinical research policies, guidance, and resources can be found on the NIMH Clinical. Research website: http://www.nimh.nih.gov/funding/clinical-research/index.shtml.

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

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

The competition for this FOA is being limited to the current awardees of the National NeuroAIDS Tissue Consortium Clinical Sites (U24), funded under RFA-MH-13-070.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

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

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

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

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

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

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

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

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

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

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

The letter of intent should be sent to:
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

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

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

NNTC Clinical Sites

Due to the complexity and time required to maintain a well-coordinated, communicative and productive research effort, a minimum effort of 3.6 person months effort to NNTC Clinical Site activities including the combined effort of potential multiple PI(s)/PD(s) is required by this FOA.

Annual Meetings

The PD(s)/PI(s) of the NNTC Clinical Sites are expected to attend an annual meeting of the NNTC Steering Committee (SC) in the Washington D.C. area, or another agreed upon locality. The meeting will also be planned and attended by the PD(s)/PI(s) of the DCC and any delegates of the DCC PD(s)/PI(s). Applicants to this FOA should include travel to the annual meeting in their proposed budget, which should include travel for themselves and a Scientific Advisor (SA). (See Section VI.2. Cooperative Agreement Terms and Conditions of Award).

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

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

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

Specific Aims

Each Clinical Site should articulate a plan for continuing resource operations including patient assessments, tissue collections, integration with the DCC, and novel recruitment strategies for enhancement of the NNTC Cohort to meet the emerging needs of NeuroAIDS investigators engaged in research.

Research Strategy

Complete applications will address each of the following components divided into the following sections with the designated page limits:

1. NNTC Overview

2. Clinical Site Functions and Operating Procedures

3. Clinical Site Collaboration with the DCC

1. NNTC Clinical Site Overview

Background and Experience. Describe the clinical site in relation to the NNTC and the experience of the site in providing CNS and PNS research resources to NeuroAIDS investigators.

Organizational Structure. Describe the governance of the clinical site in relation to the NNTC including the role of the team in responding to cohort changes and the changing needs of NeuroAIDS investigators for CNS and PNS resources.

Catchment Area. Describe the size and unique characteristics of the patient population in relation to the HIV-1 epidemic, the site cohort and enrollment goals to recruit and follow-up with site cohort participants.

Progress. Describe the progress of the site in recruiting, enrolling and following-up with NNTC cohort participants. Describe the site progress in acquiring tissue and fluid specimens from HIV-1 positive and negative individuals ante mortem, and post mortem autopsies delineating in-study and donations. Describe the site progress in providing neuropsychological, neuropathological and laboratory analysis, and supporting utilization of resources by NeuroAIDS investigators. Describe the site contributions to collaborative activities within the NNTC including effective collaboration with the DCC to provide quality controlled, de-identified clinical data to the DCC.

2. Clinical Site Functions and Operating Procedures

Applicants should provide the following details:

• Describe how the site will follow standard NNTC clinical and laboratory protocols, specimen collection protocols and data acquisition/quality control and quality assessment protocols.
• Detail site deviations from standard NNTC protocols.
• Provide details of unique site-specific strengths for performing clinical assessments and collecting specimens.
• Describe all site specific assessments that are not included in the NNTC protocols.
• Describe the recruitment and retention strategies and unique strengths of the site to enhance recruitment. While applicants should describe their enrollment plans in their applications, the final determination of the enrollment criteria for the sites will be determined by Steering Committee (SC) and NIH.
• Describe the site-specific activities for monitoring adherence to informed consent and following-up participants to monitor disease outcomes.
• Describe how the site will fully participate in SC activities including contributing to the agenda, work group activities, conference calls, teleconferences and attendance at the annual meeting.
• Provide a description of the overall strategy and operational plan including a timeline and plan for the work-flow at the Clinical Site. Include a description of the communications and organizational structure of the Clinical Site and describe any cooperative administrative arrangements involved if multiple institutions will be involved with the site.
• Describe how the specific site will contribute to and enhance the overall goals and operational goals of the Consortium.
• Describe plans to include a Scientific Advisor (SA) on the study team, preferably one who is not directly associated with the NNTC institutions and who can bring a broad and independent perspective to the NNTC.
• Describe quality control and quality assurance measures for the data, laboratory and the clinic.
• Describe how the site will facilitate access to care for HIV-1 infected patients.
• Define the process that the site will use to contribute to the current NNTC standardized assessments of neurocognitive, neurobehavioral, and other clinical status, laboratory assessments and specimen collections; include potential cost containment procedures for the structure, timing and content of tiered subject visits along with a description of the cohort structure.
• Describe how the site will address between-site differences in the subjects recruited and retained within the NNTC Cohort (demographics, language, recruitment number, length of patient enrollment and follow up), and how the site differences integrate into the Consortium.
• Discuss how collaboration and synergy with other sites will be fostered and maintained; discuss how the specific-site will interact with the NNTC SC and the DCC (See Section VI. 2 Cooperative Agreement Terms and Conditions of Award.); describe intra-site communication and decision-making practices. Each Clinical Site PD(s)/PI(s) should address how they will actively assume the responsibility and remain engaged with all SC activities and issues.

3. Clinical Site Collaboration with the DCC

To fully collaborate as a Consortium and encourage capabilities as an integrated repository of NeuroAIDS data and specimens, applications are expected to address the following:

• Detail site plans for seamless and timely collaboration with the DCC and other clinical sites affiliated with the Consortium.
• Describe the role and responsibilities of the site to ensure transfer of the clinical, specimen and site-specific specimen inventory data to the DCC including the following: data configuration requirements, checks for quality control/quality assessments, timelines to respond to DCC Data Audit and Site Visit reports and timelines for rapid sharing of data with the DCC, consistent with achieving the goals of the program.
• Describe the site plan and timeline for ensuring transfer of all NNTC-affiliated data to the DCC for storage in the NNTC database and query by NeuroAIDS investigators. The plan should include all data collected from NNTC clinical sites including assessments and in-clinic interviews, results from telephone interviews, specimen annotations and laboratory data.
• Describe plans to provide the DCC a site-specific Specimen Inventory and timelines to update the DCC with new information.
• Detail plans for maintaining the NNTC clinical database with a data dictionary which reflects the state of the science and nomenclature for the field of NeuroAIDS.
• Detail the process to be implemented by the site to respond to requests from investigators for research resources. Provide a timeline for response to the DCC after initial broadcast of the request and the timeline to ship specimens once approved.

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:

It is expected that applications will include plans for interactions with the other NNTC Clinical Sites and the DCC as well as other relevant ongoing studies of NeuroAIDS within the NNTC to maximize investments and further standardization and sharing across projects.

• All applications, regardless of the amount of direct costs requested for any one year, should address an individual Resource Sharing Plan which will then be incorporated into a consortium wide NNTC Resource Sharing Plan prior to award, consistent with achieving the goals of the program. For this FOA and the companion FOA (RFA-MH-18-251), the PD(s)/PI(s) of the NNTC Clinical Sites and DCC will collaborate with NIMH during the pre-award period to develop a consortium wide NNTC Resource Sharing Plan that will specify criteria for access to specimens, de-identified data, conditions for research use, and procedures and timelines for vetting requests for access to data maintained by the PD(s)/PI(s) of the NNTC Clinical Sites and the DCC. The consortium-wide NNTC Resource Sharing Plan and other Just-In-Time information are required prior to award. The applicant should propose a resource sharing plan in the application that takes this expectation into account.
• Applications should include information on the data dictionary, type and descriptors of data to be shared (i.e., clinical protocols and data, laboratory and research data sets), as well as a timeline for the site to reach consensus on neuropathology and neurocognitive status once the assessments are completed and a plan for data quality control, coordination, standardization, access privileges, and the schedule and timeline for release of data (time from acquisition to release to the NNTC DCC), consistent with achieving the goals of the program.
• Describe how the data from the site should be made available to the research community through publications, or public website, consistent with achieving the goals of the program.
• Describe the procedure to be followed in the event that participants withdraw consent to share their individual-level data (i.e., the timeframe and procedure for alerting the NNTC DCC to request that the specific research participant’s data should be removed from future data distributions). Should individuals previously consented by the NNTC clinical site request removal from future data distribution include a description of the procedures the site will follow to comply.

Include plans for maintenance, or transfer of ownership of the NNTC specimens and on-site NNTC-affiliated data set and database if they are to be stored beyond the funding period, as appropriate and consistent with achieving the goals of the program.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

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

Does the proposed Project address the needs of the research project that it will serve? Is the scope of activities proposed for the Project appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research resource?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Project? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing CNS and PNS resources for NeuroAIDS research? Do the investigators demonstrate significant experience with coordinating collaborative basic research? If the Project is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Project? Does the applicant have experience overseeing selection and management of sub awards, if needed? Are there key personnel in place to conduct NNTC Clinical Site operations ranging from community outreach, recruitment, enrollment and retention, clinical exams, tissue banking, autopsy, pathology, general study design and analysis, on-site computer expertise for database management, transfer of high quality data to the DCC and response to DCC data audits?

Does the application propose novel organizational concepts in coordinating the research resource the Project will serve? Are the concepts or strategies novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of management strategies proposed? Do the applicants present innovative recruitment strategies for enhancement of the NNTC Cohort to fulfill the resource needs of investigators engaged in NeuroAIDS research? Are the site clinical, laboratory, and banking plans innovative?

? Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research resource the Project will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the resource, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of human subjects? Has the site planned sufficient time to ensure appropriate oversight? Are the recruitment strategies for the end-stage NNTC Cohort feasible given the size and make-up of the cohort? Are the clinical plans for recruiting and maintaining the cohort and resource management financially feasible and well-coordinated with other NNTC Clinical Sites and the DCC? Does the site propose an organizational structure that facilitates collaboration with the DCC, the other NNTC Clinical Sites, and research investigators? If multiple institutional sites are involved does the application include a detailed description of the cooperative administrative arrangements?

Will the institutional environment in which the Project will operate contribute to the probability of success in facilitating the research resource it serves? 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 institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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

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

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

When the proposed 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 children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

Not Applicable

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

Not Applicable

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

Not Applicable

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

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

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

The NNTC Clinical Site PD(s)/PI(s) have the following primary responsibilities:

• Committing at least 3.6 person months effort (including the combined effort of potential multiple PI(s)/PD(s)) to: overseeing site-specific clinical assessment, specimen banking including the CHARTER resources and brain pathology/specimen laboratory testing activities including follow-up of subjects to determine disease outcomes; ensuring that informed consent has been conducted appropriately; fully participating in Consortium wide activities including the Steering Committee (SC) meetings, work group meetings, and teleconferences and contributing to the determination of the agenda for the annual SC meeting.
• Implementing the NNTC recruitment strategy at the Clinical Site to inform the selective enhancement of the NNTC Cohort and ensure the strategy for recruitment is responsive to the research resource needs of investigators;
• Ensuring adherence to the following NNTC SC approved protocols: clinical assessment anti mortem, laboratory analysis of specimens and autopsy and storage of the specimen resources according to NNTC standard operating procedures.
• Providing yearly progress reports which will include: each site should include their progress in meeting their targeted enrollment and recruitment goals for the prior year by providing a table to demonstrate the following information: 1) the annual change in cohort recruitment and retention including a table of the total number of cohort participants at the site including their demographics, tier status and whether they are HIV-1 positive or negative; 2) the newly enrolled recruit-to-replace participants for the prior year including their demographics, tier status and whether they are HIV-1 positive or negative; 3) the number of the NNTC cohort participants retained, lost to follow up or autopsied in the prior year and indicate whether the autopsies performed in the prior year were a) conducted on HIV-1 positive verses negative subjects; b) conducted on subjects enrolled in the NNTC study or were donated to the NNTC study; c) for autopsies conducted on-study indicate the number of ante mortem clinical assessments prior to post mortem. Each site should also include other accomplishments including the number of requests for resources that have been received, a list of the number and types of resources shipped to the investigators, the current specimen inventory, a list of publications, articles in press, manuscripts in preparation, and abstracts.
• Rapidly sharing quality controlled NNTC-related clinical data and specimen inventories with the DCC, updating the clinical data and specimen inventory within two months of data collection. Providing prompt responses to requests from investigators for NNTC-related research resources. Address any lapses in data transfer from the Clinical Site to the DCC according to the guidelines set up by the SC and communicate these lapses to NIH Program Staff within two months. NIH reserves the right to restrict funds to any NNTC clinical site on a semi-annual basis for failure to comply with the data sharing goals of the Consortium.
• Implementing policies related to the NNTC activities including publication, resource allocation, tissue request management, anti-retroviral medication reporting, and quality control/quality assurance in the collection of resources, information flow, relevant staff changes, and training.
• Using methodologies determined by the DCC (in collaboration with the SC) and in accordance with the NNTC data sharing plan, provide all clinical data, specimen annotation data, and NNTC-related research data to the DCC.
• Ensure rapid sharing of clinical, laboratory and research data and associated clinical CNS and PNS specimens according to the schedule and timeline agreed upon in the NNTC Data Sharing Plan.
• Retaining custody of and having primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

Project Scientist:

The NIMH will appoint a Project Scientist (PS). Only the NIMH PS will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants or cooperative agreements. The NIMH PS will be responsible for:

• Participating as a voting member of the NNTC SC.
• Contributing to the post award design.
• Monitoring study results and quality assurance across all sites.
• Reviewing all study protocols and data.
• Overseeing the collection, storage, and inventory along with cataloging of clinical specimens.
• Creating reports from the NNTC data for use in internal reports.

Program Officer:

• One program official from NIMH will be the assigned program officer on the cooperative agreement applications and will work closely with a program director from NINDS. Jointly, the two will be responsible for the normal scientific and programmatic stewardship of the award and will both be named in the award notice.

Areas of Joint Responsibility include:

Members of the NNTC Steering Committee (SC) include the following: NIH Program Officers and NIMH Project Scientist; the PD(s)/PI(s) of each grant award, or a designated representative in the case of a multiple PI award; and one Scientific Advisor (SA) from each clinical site. The Data Coordinating Center PD(s)/PI(s) (DCC PI), or a delegate of the DCC PI, will serve as Chair of the SC (SC Chair). Voting members will consist of each Clinical Site PD(s)/PI(s), the DCC PI or the delegate, the SC Chair (if different from the DCC PI), and the NIMH Project Scientist (NIMH PS). In the case of multiple-PD(s)/PI(s) or in the case of a delegate of the DCC PI serving as SC Chair, consensus should be reached among those PD(s)/PI(s) in casting a single vote. Decisions of the SC will be accepted by all members. The SC has the following responsibilities:

• Implementing the Consortium objectives at the Clinical Sites and updating these as needed especially in regards to updated factors for selecting subjects into the NNTC Cohort.
• Ensuring the continued allocation of the CHARTER study resources.
• Ensuring overall operations and directions of the NNTC are in keeping with very high standards, ensuring systematic assessment of priorities and timelines, suggesting improvements to the selection of the existing cohort, providing guidance on how best to accomplish quality control of clinical specimens and data, and promoting the utilization of NNTC specimens and data resources.
• Establishing and maintaining collaborative relationships that facilitate the Consortium’s objectives. These relationships include those between the Clinical Site investigators, the Steering Committee members, patient communities, the staff at the NIH institutes that are funding the NNTC, and other research communities relevant to goals of the Consortium.
• Establishing clear data sharing guidelines for the Consortium to ensure rapid transfer of all quality controlled data and specimen inventories to the DCC. Lapses in data transfer from the Clinical Site to the DCC that are longer than two months after data collection should be communicated to the SC in a timely manner. NIH reserves the right to restrict funds on a semi-annual basis for failure to comply with the data sharing timelines of the Consortium.
• Conducting an annual, full-day meeting of the SC. The meeting will be convened in the greater Washington, DC area, or other convenient location. These meetings are intended to: identify new areas of collaboration among the Consortium; decide scientific policy; address organizational issues concerning implementation and oversight of selective recruitment of the NNTC Cohort; identify gaps in the available research resources; determine the need for and memberships on working groups; and discuss issues regarding publications, access to data, interim data monitoring, and investigator access to clinical specimens and data sets. The focus of the meetings will also include: determining how the scientific and technical expertise, facilities, and other resources of the NNTC can contribute to ongoing or new projects; and sharing of data. PD(s)/PI(s) will also be expected to present their progress and discuss future strategic plans for the Consortium.
• Specifying the guidelines and procedures for the Consortium including: (1) the timely approval of requests for biological specimens, clinical data, mining of NNTC datasets, analytical assistance provided by the NNTC, and access to NNTC-related research data; (2) the timely shipment of clinical specimens to approved requestors including careful consideration to releasing specimens at risk of depletion from the NNTC tissue banks and coordinating shipments of specimens to domestic and foreign countries (i.e., meeting local and international shipping regulations and laws; assuring sample integrity for extended shipment), and following up on receipt of sample delivery along with investigator feedback; (3) contributing to the establishment and maintenance of a NNTC specimen inventory to be administered by the DCC; (4) monitoring adherence to informed consent procedures including the signatures of the NNTC participants; (5) reviewing all NNTC-related policies and documents in the first 6 months of the funding cycle, and making amendments if necessary; (5) notifying NNTC-affiliated investigators to include a Human Subjects Section if they incorporate use of NNTC resources into an NIH grant application, or if they meet the definition of an investigator in the recipient's research.
• The timely dissemination of study results to the communities involved is strongly emphasized.

Access to Data and Specimens

In view of the importance of biological specimens and data, a detailed specimen inventory including the number and types of biological specimens and clinical data should be reported to the DCC by the NNTC Clinical Sites. All requests for access to and/or release of NNTC-related specimens and/or data, whether from investigators internal or external to the NNTC, should include a detailed description of the study for which specimens are sought and the number and volume of specimens requested. Such requests should be made in accordance with a standardized NNTC Data and Specimen request form which is provided to the SC for consideration. Prior to approval and release of specimens and/or data, research plans submitted to the SC will be evaluated to determine appropriate procedures are in place for any additional human or vertebrate animal work.

Dispute Resolution

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

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Deborah Colosi, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-605-2275
Email: [email protected]

May Wong, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: [email protected]

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

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]

Tijuanna DeCoster
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9531
Email: [email protected]

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

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