Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Mental Health (NIMH) National Institute of Neurological Disorders and Stroke (NINDS)
Funding Opportunity Title	National NeuroAIDS Tissue Consortium (NNTC) Data Coordinating Center (DCC) (U24)
Activity Code	U24 Resource-Related Research Projects Cooperative Agreements
Announcement Type	New
Related Notices	April 19, 2017 - This RFA has been reissued as RFA-MH-18-251. August 17, 2012 - Frequently Asked Questions available for RFA-MH-13-071. See Notice NOT-MH-12-032.
Funding Opportunity Announcement (FOA) Number	RFA-MH-13-071
Companion Funding Opportunity	RFA-MH-13-070, U24 Resource-Related Research Project - Cooperative Agreement
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.242, 93.853
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH) and the National Institute of Neurological Disease and Stroke (NINDS) seeks applications for the Data Coordinating Center (DCC) of the National NeuroAIDS Tissue Consortium (NNTC). The DCC will function as part of the NNTC, a national resource that provides clinical and research data and biological specimens to accelerate discovery research for HIV-associated central nervous system (CNS) and peripheral nervous system (PNS) diseases. It will support the NNTC Clinical Sites that are funded via the companion FOA (RFA-MH-13-070). The DCC works cooperatively with the NNTC Clinical Sites to provide (1) management and database capabilities to ensure effective clinical and brain banking operations and (2) scientific expertise in biostatistics and HIV epidemiology to enable broad analysis of the NNTC clinical database and to aid in post award statistical analysis of recruitment and retention goals for the NNTC cohort. In this consortium, the NNTC Clinical Sites will have all patient contact which will include all clinical assessments ante-mortem. The NNTC Clinical Sites will also be responsible for the collection and housing of post mortem clinical specimens. The DCC will serve as a data repository which will include the clinical assessment data and data obtained post mortem including brain pathology reports, laboratory tests conducted on the collected specimens/fluids, a comprehensive inventory of those specimens housed at each NNTC Clinical Site, and research data, such as bioinformatics datasets.

Posted Date	July 5, 2012
Letter of Intent Due Date	August 4, 2012
Application Due Date(s)	Not Applicable
AIDS Application Due Date(s)	September 4, 2012
Scientific Merit Review	November 2012
Advisory Council Review	January 2013
Earliest Start Date(s)	April 2013
Expiration Date	September 5, 2012
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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 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

The National NeuroAIDS Tissue Consortium (NNTC) is a resource for investigators interested in conducting NeuroAIDS research to identify the neuropathogenic mechanisms involved in HIV disease of the central nervous system (CNS) and peripheral nervous system (PNS). Currently, the consortium is composed of four NNTC Clinical Sites and one Data Coordinating Center (DCC) that work cooperatively as a research resource, providing HIV/AIDS research investigators with clinically annotated datasets obtained ante mortem and associated post mortem brain tissue and fluids.

The DCC maintains a database that contains de-identified clinical information obtained from the NNTC Clinical Sites into the NNTC clinical database which includes clinical assessment data and data associated with post mortem pathology and specimens from HIV-infected and control subjects. Initially, a contract to the NNTC National Coordinating Office (NCO) provided for the convergence of the four NNTC Clinical Site databases into the NNTC clinical database. Many of the NCO functions have been subsequently incorporated into the NNTC DCC grant award in 2007 under RFA-MH-08-020. The NCO has also created a second database which has been named the, NNTC Bioinformatics Repository . Data obtained from NeuroAIDS investigators who have conducted studies with NNTC-resources has been deposited into the NNTC Bioinformatics Repository and includes nucleic acid sequence data, tissue microarray and some neuroimaging data. The DCC that is supported out of this FOA will be expected to incorporate clinical data from the NNTC Clinical Sites and research data such as bioinformatics datasets derived from NNTC resources into an integrated NNTC database.

The NNTC has been successful in acquiring specimens and data from HIV-infected and uninfected subjects. Altogether, 765 subjects have undergone clinical assessments and subsequently deceased with autopsy, thus the NNTC is able to provide well-characterized, clinically annotated CNS and PNS tissues and fluids to research investigators to conduct NeuroAIDS research. Currently, the NNTC has compiled clinical specimens that are stored at local NNTC Clinical Sites and which include brain tissue, thousands of plasma and CSF samples, and additional organs and tissues of interest. Research investigators may query the available NNTC clinical specimens and data at the NNTC website.

The NNTC has served as a valuable resource to the NeuroAIDS research community and continuation of its operations are critical given the need for high quality CNS tissues and fluids, especially those which are inaccessible to biopsy during life. It is expected that investigators using these resources will be able to examine emerging research topics in the NeuroAIDS field such as: a) eradication of HIV from persistent CNS reservoirs; b) pathogenic mechanisms of HIV-associated neurocognitive disorders (HAND) in the setting of long term HAART; and c) HIV and aging.

The key consortium wide objective for this and the companion FOA, RFA-MH-13-070, is to ensure that NNTC CNS and PNS tissue/fluids and data resources are available and useful to investigators engaged in research on HIV-associated CNS and PNS diseases. Through these two FOAs, the NIH expects to continue to fund up to four NNTC Clinical Sites (RFA-MH-13-070) and one Data Coordinating Center (RFA-MH-13-071).

The intent of this FOA is to seek applications for the NNTC DCC which will participate as part of the NNTC as described previously. The DCC funded under this FOA will be directed by a PD(s)/PI(s), who will lead the NNTC Steering Committee (SC) and as such will work in collaboration with the PD(s)/PI(s) of the NNTC Clinical Sites, a NIMH Project Scientist, and Program Staff from both NIMH and NINDS. The NNTC SC will guide the functions and processes of the NNTC as described in the terms and conditions of this cooperative agreement FOA. It is expected that the DCC will be comprised of an integrated team of investigators (within a single institution or across institutions) with (1) management expertise; (2) database expertise including management of complex datasets derived from clinical assessments and research; and (3) biostatistics and HIV epidemiology statistics.

The DCC must describe a process to integrate all NNTC-related data from the NNTC Clinical Sites and research, such as bioinformatics datasets, into a common database. Designing and implementing a procedure to upload NNTC-related data are needed to ensure that the clinical and research data are available to qualified investigators for research purposes. Data that should be accessible include: the data in the current NNTC clinical database, past NNTC-related clinical data files currently held at the NNTC Clinical Sites and NNTC-associated research datasets.

The DCC is responsible for the central management of data and, in this FOA, will serve as the data repository for the NNTC Clinical Sites. Management of data by the DCC will include data quality oversight, preparing analytical datasets to share with research investigators when they request NNTC datasets for their research, and ongoing analysis of the NNTC database. The DCC should provide a detailed plan to ensure a rapid, streamlined, and quality controlled process for data acquisition from the NNTC Clinical Sites.

The DCC should also define the manner in which research datasets are to be collected into the NNTC database from investigators who have conducted NeuroAIDS research using the NNTC resources. In addition, the research data should be standardized within the database to enable complex NeuroAIDS research data associated with the NNTC resources to be available for further inquiry. NeuroAIDS research incorporates multidisciplinary research areas including virology, neuropathology, immunology, neuroscience (molecular, cellular and integrative), genetics, genetic epidemiology, and biostatistical research. The DCC should develop a database management system (DBMS) that accomodates multidisciplinary research areas and which can be made readily accessible to research investigators. The DCC is encouraged to utilize databases that have the capability for potentially integrating with other large NeuroAIDS databases. Where feasible, a federated database model is encouraged in which database systems relevant to the field of NeuroAIDS are mapped to the NNTC database, yet remain autonomous and geographically decentralized.

Governance of the NNTC

The NNTC will be governed by the NNTC Steering Committee (SC). Details on the composition and function of the Steering Committee are provided in Section VI.2. Cooperative Agreement Terms and Conditions of Award.

Funding Instrument	Cooperative Agreement
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIMH and NINDS intend to commit approximately $600,000 in FY 2013 to fund 1 award.
Award Budget	Budgets for direct costs may not exceed $600,000 per year.
Award Project Period	The total project period for an application submitted in response to this FOA may not exceed five years.

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.

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Foreign Institutions

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 must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least4-6 weeks prior to the application due date.

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Applications for the DCC Open Competition (U24) may not be submitted by the 4 institutions that represent the current 4 NNTC clinical and banking sites.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 Application Guide, 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.

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 research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Dianne Rausch, Ph.D.
Division of AIDS Research
National Institute of Mental Health (NIMH)
6001 Executive Boulevard, Room 6105, MSC 9616
Rockville, MD 20892-9616
Telephone: 301-443-6100
Email: [email protected]

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Jean Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD 20892-9609
Telephone: 301-443-3367
FAX: 301-443-4720
Email: [email protected]

All page limitations described in the PHS398 Application Guide and must be followed, with the following requirements:

• Specific Aims section is limited to one page maximum.
• Research Strategy section is limited to 12 pages including tables, graphs, figures, diagrams, and charts

NNTC Clinical Site Visits

The PD(s)/PI(s) of the DCC will schedule NNTC Clinical Site visits to perform training, data audits, and data management at local sites on a yearly basis. Applicants to this FOA will include travel to the NNTC Clinical Sites in their proposed budget. (See Section VI.2 Cooperative Agreement Terms and Conditions of Award).

Annual Meetings

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

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Specific Aims (Not to exceed 1 page)

The specific aims should include management strategies and processes for efficient database operations to ensure effective clinical and brain banking functions. The PD(s)/PI(s) should articulate plans to conduct ongoing biostatistical and epidemiological analysis of the NNTC database to feed back information to the NNTC Clinical Sites to guide recruitment of new subjects into the cohort and to the research community at large to inform new hypothesis driven research.

Research Strategy Section (Not to exceed 12 pages)

Responsive applications will address each of the following components (Page numbers indicated below are provided only as guidelines):

1. DCC Overview - Page 1

2. DCC Management Capabilities - 1-4 pages

3. DCC Database Capabilities - 1-4 pages

4. DCC Scientific Expertise in Biostatistics and HIV Epidemiology - 1-2 pages

5. DCC Collaboration with the Steering Committee and NNTC Clinical Sites - 1-2 pages

DCC Overview

The Overview should include background information regarding the overall DCC approach to working cooperatively to serve as a consortium wide and national resource to the scientific community engaged in NeuroAIDS research on HIV-associated central and peripheral nervous system disease by providing (1) management expertise to ensure effective clinical and brain banking operations; (2) database expertise including management of complex datasets derived from clinical assessments and research; and (3) scientific expertise in biostatistics and HIV epidemiology for analysis of the NNTC database to aid in post award statistical analysis of recruitment and retention goals for the NNTC cohort and to inform new hypothesis driven NeuroAIDS research.

The overview should also include plans to obtain and place all past, current, and future NNTC-related data from the NNTC Clinical Sites and NeuroAIDS investigators into the public domain to ensure the clinical and research data is available to qualified investigators engaged in analysis of the natural history of HIV-associated CNS and PNS diseases.

DCC Management Capabilities

Describe plans and activities to meet and fulfill the DCC-specific activities and goals of the DCC, which include:

• Enabling the DCC to support and collaborate with the NNTC Clinical Sites, NNTC Steering Committee, and NeuroAIDS investigators to yield a research resource capable of providing access to clinical specimens, NeuroAIDS research data, and tools to accelerate discovery research for HIV-associated central nervous system and peripheral nervous system diseases.
• Ensuring logistical support and management to fulfill the DCC tasks including, but not limited to: conducting monthly teleconferences of the Steering Committee and work groups, writing, organizing and distributing NNTC-related reports including regular conference calls of the SC, annual meetings of the SC, other work groups and reports that may be requested by the NIMH Project Scientist and NIH Program Staff; coordinating and archiving information regarding NNTC activities; and producing any NNTC-related resource reports.
• Serving as an information conduit between the consortium members, scientific community being served, and layman public audiences by producing appropriate public-relations materials on behalf of the NNTC. This includes updating, and advertising a public NNTC website, actively promoting broad utilization of NNTC resources by outside investigators, and providing toll-free telephone access by which researchers may contact the DCC.
• Collecting requests from researchers for specimens and data, distributing requests to individual NNTC Clinical Sites, coordinating the approval of requests in a timely manner with the Steering Committee, coordinating shipments of samples, and following up on receipt of tissue and fluid delivery.
• Maintaining and distributing a list of all publications, manuscripts in progress, abstracts, and presentations for which NNTC data and/or clinical specimens are involved. Maintaining a searchable web-based archive of NNTC publications. Providing a forum for posting, circulating and consolidating input on drafts of manuscripts by consortium participants.
• Coordinating and providing access to NNTC datasets for presentations and publication of study-wide data.
• Monitoring adherence to clinical and laboratory protocols across the clinical sites, and coordinating implementation of any new or modified protocols that the SC approves during the course of the project.
• Preparing and updating operations manuals and data collection forms, as well as coordinating the revision of existing NNTC questionnaires, and the development and testing of new questionnaires for utilization by the NNTC Clinical Sites, including the standardization of procedures for data collection.
• Preparing a quarterly NNTC public-use data (PUD) electronic file covering the data collection period. All collected variables must be provided in a widely useable format with appropriate, complete data dictionaries to accompany the data.
• Providing the research community with a better understanding of the strengths, limitations, and flexibility associated with research projects based on NNTC collections.

3. DCC Database Capabilities

Provide a description for the DCC-specific capabilities that will allow the DCC to fulfill the primary objectives, which include:

• Maintaining the centralized NNTC database on a secure network server that contains unidentifiable patient-related information (such as cognitive status, drug use history, neuropsychological history, and CD4 count), general demographics, and pathological data. The NNTC data management system should be capable of processing and retrieval of NNTC-related data, capable of facilitating the rapid transfer, editing, cleaning, quality, reporting, and storing for query of data. The NNTC database should have a data dictionary appropriate to the research of HIV-associated central and peripheral nervous system disease that is able to be updated with new terminology as the field of NeuroAIDS progresses. Inclusion of the following datasets into the NNTC database is expected: the central NNTC clinical database and past NNTC-related clinical and specimen data files currently held at NNTC Clinical Sites since 1998. Applicants are also encouraged to plan for inclusion of the NNTC Bioinformatics Repository implemented by the National Coordinating Office (NCO), and future NNTC-associated biomedical research datasets into a NNTC database with the capacity for being scalable, extensible, and federated.
• Maintaining and monitoring a password-protected website accessible to authorized users.
• Providing a detailed plan to ensure a rapid, streamlined, yet quality controlled process for data acquisition from the NNTC Clinical Sites and biomedical investigators engaged in studies which utilize the NNTC resources.
• Training consortium staff and NeuroAIDS investigators in any new database entry method that results from Steering Committee approved changes in database operations. Providing technical assistance related to data transfer.
• Describing the role, responsibilities, requirements, and timelines of the DCC for rapid placement of all NNTC Clinical Site-related data obtained from clinical assessments, telephone interviews, and specimen annotations from the longitudinal databases into the public domain via the DCC, according to the "Cooperative Agreement Terms and Conditions of Award" outlined in Section VI.2, and in collaboration with the NNTC Clinical Sites, including responsibilities, effort, requirements for collaboration with the NNTC Clinical Sites, and timelines.

4. DCC Scientific Expertise in Biostatistics and HIV Epidemiology

Describe how the DCC will:

• Provide the scientific expertise in HIV epidemiology and biostatistics to support analysis of the NNTC database on behalf of NeuroAIDS investigators.
• Conduct post award statistical analysis of recruitment and retention goals for the NNTC cohort.
• Perform on-going database-derived scientific analyses for the NNTC Clinical Sites to guide ongoing recruitment of new subjects into the cohort and identify gaps in the available NNTC resources as determined by investigator requests, inform reports for the SC and NIH Program Staff, generate descriptive statistics for the public website and provide reports to the research community at large that may inform new hypothesis driven research.
• Facilitate query and statistical analysis of the NNTC database by research investigators.

5. DCC Collaboration with the Steering Committee and NNTC Clinical Sites

Address plans to:

• Work collaboratively with the Steering Committee, the NNTC Clinical Sites, a NIMH Project Scientist, and Program Staff from both NIMH and NINDS.
• Collaborate with the NNTC Clinical Sites to provide, update, and maintain a detailed NNTC Specimen Inventory according to the guidelines specified by the Steering Committee. Coalesce data from each NNTC Clinical Site and provide an annual summary of the NNTC Specimen Inventory in annual Project Reports to NIH.
• Present clinical specimen requests from NeuroAIDS investigators to the Steering Committee according to the procedure and timelines specified by the SC.
• Remain responsive to the Steering Committee which governs the NNTC. Note that all activities of the NNTC must be reviewed, discussed, and shaped by the SC.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398 Application Guide, with the following modifications:

It is expected that applications will include information on the following aspects of data coordination, standardization, and sharing:

• Plan for interactions with other relevant ongoing studies of NeuroAIDS and plans to serve as a consortium wide and national resource to maximize investments and further standardization and sharing across projects

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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

NIMH will hold a pre-application teleconference on Tuesday, July 17, 2012 from 11:00am - 12:00pm (EST) to which all prospective applicants are invited. This is a technical assistance teleconference conducted by NIMH staff involved in managing this program to explain the goals and objectives of this initiative and answer questions from the attendees. Participating in the teleconference is neither required nor necessary for a successful application. It is intended to be an opportunity to clarify the objectives of the initiative. Potential applicants are encouraged to submit their questions or comments to [email protected] in advance of the call. Applicants interested in participating in the technical assistance call should send a message to the mailbox above to obtain a dial-in number. A set of Questions and Answers from the teleconference will be posted after the session on a site-to-be-determined and announced.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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/priority 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? 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? Does the DCC fulfill other roles and duties that are critical to the success of the NNTC and to the work of external collaborators?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Are the expertise and commitment of the PD(s)/PI(s) and other key personnel adequate for the required scope and objectives of the NNTC DCC? Have the PD(s)/PI(s) demonstrated sufficient leadership in coordinating tissue banking activities across multiple institutions? Are there key personnel in place to conduct NNTC operations ranging from biomedical statistician to managing specimens, managing websites, and transferring all NNTC-related data from the clinical sites to the DCC? Has the PD(s)/PI(s) successfully served in the capacity of a data management and analysis center in the past? Do the PD(s)/PI(s) have experience with database platforms with the capacity for being federated? Have the PD(s)/PI(s) budgeted sufficient time to ensure appropriate oversight of the NNTC DCC?

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? Do the PD(s)/PI(s) propose innovative approaches and practices in data and inventory management systems, federated database capacity, and communications in support of the clinical and banking operations?

Approach

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

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Have the PD(s)/PI(s) appropriately addressed the responsibility of developing the logistics and communications that are necessary to coordinate the NNTC activities? Has the application demonstrated how appropriate training will be conducted to ensure rapid, high quality data collection, submission to the database, and query of the database? Is the approach for working with the NNTC site PD(s)/PI(s) and Steering Committee members reasonable and synergistic?

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? Does the environment in which the work will be done contribute to the probability of the success of the NNTC DCC and PD(s)/PI(s) in addressing the multifaceted responsibilities?

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

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/priority score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and 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 and the National Advisory Neurological Disorders and Stroke 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(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• Developing a plan for ongoing analysis of data generated by clinical and pathological assessments provided by the NNTC Clinical Sites to ensure that the recruitment and retention of the NNTC cohort remains statistically powered to achieve the priorities and to identify gaps in the available resources as determined by investigator requests.
• Providing scientific expertise in biostatistics and HIV for all aspects of the DCC operations where the expertise is needed, including analysis of the NNTC database as needed.
• Implementing policies related to the NNTC activities including publication, resource allocation, tissue request management, and anti-retroviral medication reporting which have been approved by the SC.
• Implementing and maintaining a detailed system for tracking the NNTC Clinical
  Site data and specimen inventory. The DCC will obtain data and specimen inventories within two months of collection at the NNTC Clinical Site. Any lapses in data transfer from the NNTC Clinical Sites to the DCC should be communicated and dealt with according to the guidelines set up by the SC and communicated to the NNTC Clinical Sites and NIH Program Staff within two months. NIH reserves the right to restrict funds on a semi-annual basis for failure to comply with data sharing goals of the consortium. The DCC will provide a Clinical Site-specific and consortium wide Specimen Inventory for inclusion in an annual progress report to the SC, NIMH, and NINDS Program Staff.
• Enabling rapid receipt, quality control and assurance, and investigator access to all NNTC-related clinical datasets and specimen annotated data held in the NNTC database.
• Providing logistical support for the consortium including distributing documentation and writing meeting summaries for the regular conference calls of the SC, annual meetings of the SC, and other committees.
• Organizing, attending and leading the annual SC meetings.
• Designing methodologies and providing training support, to transfer all NNTC Clinical Site data and specimen annotations dating back since 1998 to the DCC within one year of the notice of grant award according to data sharing policies.
• Scheduling NNTC Clinical Site visits to perform training, data audits and data management at NNTC Clinical Sites on a yearly basis.
• Management of NeuroAIDS investigators' requests for specimens and data with the SC, prioritizing requests for samples, and facilitating delivery of samples to investigators in a timely manner.
• Providing an annual progress report which should include an updated NNTC Specimen Inventory, a table summarizing the active NNTC cohort, the number and types of specimens collected at the NNTC Clinical Sites, the number of requests for resources, the amount of time lapsed from receipt of requests for resources and approval/denial by the Steering Committee, the number and quantity of specimens actually shipped to investigators, identification of gaps in NNTC research resources, reports of problems in data collection, record abstraction and information flow, and a summary of the statistics and epidemiology activities including an annual analysis of the NNTC database.
• Providing centralized storage, security, processing and retrieval of NNTC data within a data management system and ensure its adequacy for the expanding needs of the NNTC including facilitating the rapid transfer, editing, cleaning, quality, reporting, and storing for query of data collected from NNTC Clinical Sites.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current 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:

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 Steering Committee.
• Contributing to the post award design of the broad consortium wide scientific priorities.
• Monitoring study results and quality assurance across all sites.
• Reviewing all study protocols and data.
• Overseeing the collection, inventory, storage and cataloging of samples.
• Creating reports from the NNTC data for use in internal reports.
• Additionally, an agency program official from NIMH and one program director from NINDS will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

NNTC Steering Committee (SC): NIMH PS, 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 NNTC clinical site identified as important to the consortium wide, broad scientific priorities will be members of the SC. 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 the clinical site PD(s)/PI(s), the DCC PI or the delegate SC Chair (if different from the DCC PI), and the NIMH PS. In the case of multiple-PD(s)/PI(s), consensus should be reached on their position to cast a single vote representative of their site. Awardee members of the NNTC will be required to accept and implement policies approved by the SC. The members of the SC will be responsible for:

• Ensuring that recruitment strategies for the cohort are implemented at the NNTC Clinical Sites and updated as needed to selectively enhance the cohort composition and ensure the availability of CNS and PNS research resources to NeuroAIDS investigators.
• Ensuring overall operations and directions of the NNTC are in keeping with the high standards of scientific and programmatic achievement including ensuring adequate mechanisms for systematic assessment with priorities and timelines, improvements to the status of the existing cohort, quality control of clinical specimens and data, and promoting utilization of NNTC specimens, data, and analytical resources by investigators inside and outside of the consortium.
• Establishing and maintaining collaborative relationships that facilitate the achievements of the consortium’s objectives with the NNTC Clinical Sites, the Steering Committee, patient communities, the NIH institutes funding the NNTC, and other research communities relevant to neurocognition.
• Promoting and specifying the guidelines and procedures for the consortium including: (1) clear and specific details and timelines for SC consideration and approval of requests for biological specimens, mining of NNTC datasets, analytical assistance provided by the NNTC, and NNTC-related research data; (2) specifications for rapid access and priority release of clinical specimens by the Clinical Sites and for those specimens at risk of depletion from the NNTC tissue banks; (3) specifications for the establishment of a NNTC Specimen Inventory to be administered by the DCC and into which a count of specimens and datasets available to investigators is kept; and (4) monitoring adherence to informed consent signed by NNTC participants.
• Establish policies for the NNTC activities including publication, resource allocation, tissue request management, and anti-retroviral medication reporting which have been approved by the SC.
• Attending and participating in an annual, full-day meeting of the SC with the NNTC SC, the NIMH PS, and NIH Program Staff. The meeting will be convened in the greater Washington, DC area, or other convenient location, to decide all scientific policy and issues related to alterations or implementation of the broad, consortium wide scientific priorities, organizational structure, communications, working group memberships, publications, access to interim data monitoring, and access to data, biological specimens, or analysis of the data. If there areas of joint responsibility (examples include membership, duties, voting, steering committee, etc.), revise text as appropriate.

Dispute Resolution:

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

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) 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.

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3012
Email: [email protected]

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

David Armstrong, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
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 Parts 74 and 92.