FAQs for RFA-MH-13-070: Limited Competition: National NeuroAIDS Tissue Consortium (NNTC) Clinical Sites (U24)

Should the specific targets of recruitment for the NNTC cohort be determined before the submission and included in the grant application, or will they be determined by the NNTC Steering Committee?

This Funding Opportunity Announcement (FOA) encourages developing recruitment strategies to enhance the NNTC cohort. Each NNTC Clinical Site application should include in the application a plan for recruiting participants to enhance the NNTC cohort. The Cooperative Agreement Terms and Conditions of Award indicates that each Clinical Site is responsible for implementing the NNTC recruitment strategy to inform the selective enhancement of the NNTC cohort and ensure the strategy for recruitment is responsive to the resource needs of research investigators; ensure rapid sharing of clinical data and associated clinical central nervous system (CNS) and peripheral nervous system (PNS) specimens; and ensure analysis of the resources according to NNTC standard operating procedures. The Steering Committee (SC) will have the responsibility for implementing the Consortium objectives at the Clinical Sites and updating these as needed especially with regard to updating factors for selecting subjects into the NNTC cohort.

Can NNTC clinical site budgets be used to support pilot projects?

No. The NNTC Clinical Sites FOA does not support research.

Why does the FOA mention that NNTC Clinical Sites should “help” address the research area of eradication of HIV from persistent CNS reservoirs?

Three emerging program priorities of NIMH and NINDS are listed in Part 2. Section I of the FOA, one of which is the eradication of HIV from persistent CNS reservoirs. Applicants are encouraged to develop recruitment strategies with these program priorities in mind. In this manner, the funded Clinical Sites will "help" by recruiting subjects who will contribute to the collection and availability of resources that are needed and relevant to the three emerging research areas in the NeuroAIDS field.

Should applicants include committees, such as a neuropathology committee, in the application? If so, how will these functions be paid for?

In the Research Strategy section of the application, under "Clinical Site Functions and Operating Procedures", applicants are advised to define the process the site will use to contribute to the current NNTC standardized assessments of neurocognitive, neurobehavioral, and other clinical status, laboratory assessments and specimen collections. Such a process may, or may not, include the development of a committee to consider potential changes to the standardized assessments and provide advice to the Steering Committee. These activities, including the cost of a committee or committees, should be included in the proposed budget for each site.

Should applicants assume that the NNTC Data Coordinating Center (DCC) will be providing the database and programming support for all local sites? Should applicants to the Clinical Sites FOA discard the local databases except for proprietary data?

No. The key objective listed in the NNTC Clinical Site FOA is to pursue the continued operations of the NNTC Clinical Sites including maintaining local site databases and provision of programming support for clinical data with patient identifiers. The DCC maintains a database that contains de-identified clinical information obtained from the NNTC Clinical Sites.

Does NIMH want the sites funded by the FOA to upload data that may have been collected on paper charts from the past 15 years, but was not entered into the database?

Yes. The FOA indicates that all data since 1998 should be transferred to the DCC, where feasible. Although the extent of data capture from the prior awards is at the discretion of the applicants, the secondary goal of the FOA is to ensure that all data are deposited into the NNTC database to make them available to the research community. In general, capturing the abundance of data from the Clinical Sites and from research conducted with NNTC resources will increase the value of the NNTC dataset.

Are the research activities in the currently funded NNTC Clinical Site awards relevant to the current FOA and, if so, should they be included in the application?
Yes. The FOA (U24) indicates that applicants should also include accomplishments from the previous award period (U01) in the Research Strategy section under “NNTC Overview” of the application.

Clarify the scope of the Scientific Advisor’s (SA) role and the time commitment expected. Does each NNTC Clinical Site application need to budget for an advisor and if so, how much salary should be allocated in the budget? Is a letter from the proposed advisor required to be submitted with the application?

The SA is intended to bring a broad and independent perspective to the NNTC, particularly in light of the rapidly changing manifestations of HIV-associated complications of the nervous system in the era of HAART. In addition, one SA from each clinical site will be included as a non-voting member of the NNTC Steering Committee. A letter from the intended SA is not required in the application. The FOA does not specify the scope of the role, time commitment, or budget requirements for the SA beyond the need for applicants to include travel for the SA in the proposed budget.

Do NIMH and NINDS require applicants to include a SA?

NIMH and NINDS have noted that SAs have made strong contributions to the consortium in the past. While the institutes do not require inclusion of a SA in the application, one is strongly recommended.

What is meant by the following sentence in the FOA: "Provide the number of annual autopsies collected by the site and identify whether they were conducted as part of the NNTC clinical protocol or outside of the NNTC clinical protocol"?

Applicants are advised in the Research Strategy section, under NNTC Overview, to classify autopsy reports based on whether the autopsies were collected from subjects who have been enrolled in the NNTC cohort as part of the NNTC clinical protocol. Autopsies obtained from HIV-positive or HIV-negative subjects who wished to participate in organ donation yet have never been enrolled in the NNTC cohort are considered to be "outside" of the NNTC clinical protocol.

Clarify what information is needed to address the following in the application: "between-site differences in the subjects recruited and retained within the NNTC cohort".

The current NNTC Clinical Sites are geographically distributed across the country. It is anticipated that each site will be unique with regard to the characteristics of subjects recruited. Examples of unique site characteristics include, yet are not limited to, the following: demographics, language spoken, recruitment number, length of patient enrollment and follow up. Applicants are encouraged to highlight any differences from other sites in the subjects recruited and retained within the NNTC cohort. Applicants should also justify how the site differences in subject characteristics reflect the recruitment strategy for the NNTC cohort.

Clarify how the following guidance differs from the standard operating procedure currently in effect at the sites: "plan to provide the DCC a site-specific Specimen Inventory".

The FOA specifies in The Cooperative Agreement Terms and Conditions of Award, under Access to Data and Specimens, that all access to and/or release of NNTC-related specimens and/or data, whether from investigators internal or external to the NNTC, require prior approval by the SC. In the prior award period, Clinical Site Principle Investigators (PIs) were allowed to retain half of the clinical specimens for local research efforts and were allowed to distribute that half to research investigators without consulting the SC. In addition, Clinical Site PIs were only required to submit ten percent of the clinical data to the DCC in the prior award. In this FOA, the Clinical Sites should include a plan in their application that ensures the DCC will receive an up-to-date inventory of all NNTC-derived data and specimens in a timely manner.

Does the FOA specify that additional assistance to the individual Clinical Sites will be provided (i.e., statistics, programming)?

Regarding statistics, in the Cooperative Agreement Terms and Conditions of Award section of the DCC FOA, under "The Data Coordinating Center PD(s)/PI(s)", applicants are advised to provide the following scientific expertise in HIV epidemiology and biostatistics: (1) support analysis of the NNTC database on behalf of NeuroAIDS investigators; (2) conduct post award statistical analysis of recruitment and retention goals for the NNTC cohort; (3) perform on-going database-derived scientific analyses for the NNTC Clinical Sites to guide ongoing recruitment of new subjects into the cohort; (4) identify gaps in the available NNTC resources as determined by investigator requests and inform reports for the SC and NIH Program Staff; (5) generate descriptive statistics for the public website and provide reports to the research community at large that may inform new hypothesis driven research; and (6) facilitate query and statistical analysis of the NNTC database by research investigators.

Regarding programming, in the Cooperative Agreement Terms and Conditions of Award section of the DCC FOA, under the "Areas of Joint Responsibility", applicants are advised to provide training to consortium staff and NeuroAIDS investigators in any new database entry method that results from Steering Committee approved changes in database operations. In addition, DCC FOA applicants are advised to provide technical assistance related to data transfer.

Other than where specified in the DCC FOA, Clinical Site applicants will be expected to conduct their own statistical analyses and programming.

Will Clinical Site applicants be required to include DNA extracted from clinical biological fluids and tissues as a research resource?

No. Applicants are not required to include DNA extracted from clinical specimens as a research resource.

Are paper applications expected?

Yes. 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 the 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. See Section IV, number 2, for more details. In the notice, NOT-OD-07-018 , applicants are encouraged to send Appendix materials submitted with paper PHS 398 applications on a compact disc (CD) in PDF format in lieu of the five collated sets. See application instructions for details on preparing CDs. Only a single CD need be sent.

For additional questions, please contact:

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: drausch@mail.nih.gov

Jeymohan Joseph, Ph.D.
Division of AIDS Research
National Institute of Mental Health (NIMH)
6001 Executive Boulevard, Room 6105, MSC 9616
Rockville, MD 20892-9616
Telephone: 301-443-3012
Email: jjeymoha@mail.nih.gov

May Wong, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: wongm@mail.nih.gov