Restructuring the NIAID Clinical Trials Networks

It is anticipated that NIAID will award at least 25 CTUs through this Funding Opportunity Announcement (FOA). However, we will fund the number of CTUs necessary to ensure that each of the NIAID HIV/AIDS clinical research networks has the clinical research sites needed to accomplish its scientific agenda.

NIAID will consider the scientific and technical merit of the proposed applications as determined by scientific peer review, availability of funds, programmatic priorities, and geographic distribution of the proposed Clinical Research Sites (CRSs) to determine awardees. NIAID reserves the right to fund partial components, as defined by the FOA, of an application.

No. Quotas have not been established for CTUs or CRSs by geographic location or research area. NIAID reserves the right to limit the number and types of CTUs and CRSs that are appropriate to support the NIAID clinical research networks.

No, NIAID clinical research network grant awardees will not be known by CTU applicants prior to the CTU application deadline. CTU applicants should propose CRSs and affiliation with the clinical research areas as posted in the Network Leadership Group FOAs.

Yes. Eligible domestic (U.S.) or international organizations can be

• A CTU, with one or more domestic CRSs
• A CTU, with one or more international CRSs
• A CTU, with a mix of domestic and international CRSs
• A CRS affiliated with a domestic CTU
• A CRS affiliated with an international CTU

Yes. All applicants, including USG agencies interested in applying for CTUs, will be expected to compete through this FOA. We expect the only difference between successful USG and non-USG agency applications to be the mechanism of funding.

Awardees under this FOA are eligible to work on projects funded by other USG agencies and do not require NIAID permission to do so. Applicants currently participating in such projects (e.g., PEPFAR) should indicate relevant activities when describing their experience in the application. Successful applicants must indicate if any scientific or budgetary overlap among projects exists at the time of award and must work with NIAID to negotiate how to eliminate this overlap.

No. Applications must follow the formatting guidelines set forth in the PHS 398 instructions. Applications that do not conform to these specifications will be returned without review.

There can be more than one CTU application from a single organization/institution, provided that each application is scientifically distinct. CTU applicants should provide adequate scientific justification for proposing more than one CTU from a single institution in each of the applications proposed. NIAID reserves the right to combine components submitted in multiple applications from a single institution into a one award.

The number of CABs within a given CTU is a decision best made by the CTU applicant. This decision should take into account the role of the CAB in representing the local community participating in the clinical research and the geographic and cultural diversity of the CRSs.

Yes, participants can be seen in different parts of the same institution and still be considered part of the same CRS. We encourage a model of "self-assembly" based on your organizational circumstances, as there are many nuances to what constitutes one discrete CRS from another. Please refer to the CRS definition in the FOA document for details; however, the goal is to encourage consolidation, where possible and practical, so that efficiencies can be recognized. Factors to consider in determining whether a CRS should be a discrete entity include: institutional affiliation, extent of resources shared (staff, clinic, pharmacy, lab, regulatory), geographic location, leadership of the CRS, and scope of IRB authority. If resources can be coordinated efficiently and shared across two or more locations within the same institution without compromising study conduct and performance, then consolidation into one CRS is highly encouraged.

Satellite sites should not be discussed in this application. Satellite sites (like protocol-specific sites) will be identified after award as necessary, based on identified protocol-specific clinical research network needs.

The applicant’s response to Component 1 (CTU Research Overview) is limited to 30 pages. Responses to each of the other components (2 through 11) are limited to an additional number of pages as specified in the FOA for those individual components. For example in response to Component 1, an applicant can write up to 30 pages; in response to Component 2, the applicant can write up to 12 pages; and in response to Component 10 (assuming the applicant proposes 3 CRS), the applicant can write up to 36 pages (12 pages for each CRS proposed).

No, the response as to capability to participate in the Clinical Research Network on Antibacterial Resistance is a stand-alone item in the application. Applicants’ discussions of their interest and capacity to participate in the Clinical Research Network on Antibacterial Resistance should be limited to component 11 (Clinical Research Network on Antibacterial Resistance) of the FOA. Applicants are not expected to include their proposal to work in this network in the table and/or discussions in component 1 (CTU Research overview) or in the descriptions of each CRS (maximum of eight) in component 10 (Clinical Research Sites).

No, a CTU as proposed will not be competitive. Responsive CTUs to this FOA will be robust, integrated research units comprised of one to eight CRSs and must participate in a minimum of two HIV/AIDS Clinical Research Networks. CTUs which propose to affiliate with the Network on Integrated Strategies to Prevent HIV Infection must have the capacity to contribute to a broad range of activities within the scientific priority areas described in the FOA (RFA-AI-12-011), many of which will require a clinical setting to conduct the research. These scientific priority areas include the following two areas:

1. Evaluate and optimize integrated strategies to prevent HIV infection
2. Evaluate and optimize most promising pre-exposure prophylaxis (PrEP) regimens

After the successful CTU applicants have been identified, if the capacity and population for a specific study does not exist within the funded portfolio of NIAID CTUs/CRSs, there is a mechanism for limited expansion of sites to meet the needs of a specific protocol. This mechanism is described in Part 2, Section 3 ("CTU Structure and Function") of the CTU FOA.

Two sites from different institutions cannot combine to make up one CRS simply to satisfy the enrollment or other performance requirements established by NIAID and/or the Clinical research networks. Please refer to the CRS definition in the FOA document for details. Although applicants are encouraged to consolidate where possible and practical, the benefits of the proposed configuration as well as the efficiencies recognized should be evident in the application. Factors to consider in determining whether multiple components constitute a single CRS entity include: institutional affiliation, extent of resources shared (staff, clinic, pharmacy, lab, regulatory), geographic location, organizational structure, leadership of the CRS and scope of IRB authority.

After successful awards have been made in response to this solicitation, protocol specific needs may arise which cannot be met by the existing CRSs, thus presenting a limited opportunity to engage additional site locations and to meet the specific protocol required need. Such additional site locations will be expected to close at the conclusion of the protocol.

The CTU is an organization/institution responsible for coordination and oversight of clinical trials in accordance with the clinical research network, NIAID and other applicable policies and as such it is not interchangeable with a CRS and cannot be proposed as part of another CTU. The CTU is comprised of distinct, physical components such as pharmacy, laboratory, and clinical research sites (CRS). As noted in the FOA, an individual CRS and/or CRS Leader may be proposed in only one CTU application.

Although an institution/organization may propose more than one CTU application, each application must contain justification for such needs. CRSs within an institution/organization that are aligned with different institutions/organizations other than theirs must provide evidence of the practical efficiencies that will be recognized by this alignment.

As mentioned in the FOA, NIAID favors a model of self-assembly and we encourage consolidation where possible and practical, with the goal of recognizing efficiencies and containing costs within the Clinical Trials Unit. We strongly encourage careful consideration of consolidation for the sole purpose of satisfying enrollment or other performance requirements established by NIAID and/or the clinical research networks if there are no practical efficiencies, reduction of redundancies, or cost containment measures achieved. The benefits of the proposed configuration as well as the efficiencies recognized should be evident in the application. Factors to consider in determining whether multiple components constitute a single CRS entity include: institutional affiliation, extent of resources shared (staff, clinic, pharmacy, lab, regulatory), geographic location, organizational structure, leadership of the CRS and scope of IRB authority.

After successful awards have been made in response to this solicitation, protocol specific needs may arise which cannot be met by the existing CRSs, thus presenting a limited opportunity to engage additional site locations and to meet the specific protocol required need.

There are several questions and answers within this Q&A that pertain to the definition and composition of a Clinical Research Site (CRS) that may be helpful to you.

Although there is no upper limit to the number of Principal Investigators/Program Directors (PIs/PDs) that can be named in an application, applicants should carefully consider alignment of roles, responsibilities and scope of authority of individuals named as PD/PIs. Applicants must provide a Leadership Plan if they propose multiple PIs/PDs, and the plan must clearly define how authorities and accountabilities are aligned, plans for decision-making, and communication across the multiple PIs/PDs, in addition to other requirements outlined in NIH Grants Policy (see link below). Each PD/PI named in a multi-PI/PD application is responsible for the proper conduct and management of the entire CTU, and must be able to run the operations of the entire CTU. The number of PD/PIs should be well justified and not exceed the number required for efficient management of the CTU.

Additional information on multiple PD/PIs is available at: Frequently Asked Questions: Multiple Principal Investigators

We expect applicants to provide a cover page as an "administrative separator" between each of the components. This cover page will not count towards the page limits. Something as simple as "Component 5 – Evaluation" is all we expect to see.

The protocol inclusion enrollment report form is not a requirement for applications responsive to the CTU FOA because the applicants are proposing infrastructure for the NIAID Clinical Research Network Leadership grants, and are not requesting funding for any specific clinical trials as part of the CTU FOA application. Applicants are expected to mention past or current clinical research work in support of the past performance and capacity criteria; however, inclusion enrollment reports for any trial(s) referenced in the application is not a requirement.

NIH policy prohibits NIH institutes from sharing applicant information. NIAID will not be providing public access to the content of the LG applications. CTU applicants are encouraged to review the research priority areas for each of the LG FOAs as they develop their applications. Each of the six LG FOAs can be accessed by visiting Restructuring the NIAID Clinical Trials Networks

The maximum number of pages for a CTU with 4CRSs is 156 broken down as follows:

Component 1 30 pages
Component 2 12 pages
Component 3 6 pages
Component 4 6 pages
Component 5 6 pages
Component 6 12 pages
Component 7 12 pages
Component 8 12 pages
Component 9 12 pages
Component 10 96 pages (up to 12 pages each per up to 8 CRS)

 

The determination of whether or not the CTU PD/PI can also be designated as a CRS Leader for any given CTU will depend on the size and scope of the CTU. An individual is not specifically prohibited from serving simultaneously in both roles however, the experience, qualifications and extent to which the PD/PI and /or CRS Leader is committed to other activities should determine the appropriateness of that decision.

Please refer to the glossary of acronyms and terms for a full description of the DAIDS Enterprise System (DAIDS-ES). The DAIDS- ES includes multiple modules with which the DAIDS clinical trials networks (including CTUs) are required to interact. These modules include, but are not limited to: Adverse Experience Reporting and Processing System, Clinical Site Monitoring, and Protocol Registration. Applicants should outline their overarching strategies for interacting with one or more of these modules across the multiple components of their CTU. For example, describe how resources will be aligned to interact with these modules to support timely and efficient communication.

Please refer to the glossary of acronyms and terms for the full description of HANC. HANC provides coordination for many network wide initiatives and the clinical research networks (including CTUs) are integral to the success of the collaborative efforts of HANC. Applicants are encouraged to explain their plans for communicating and collaborating with HANC including willingness to participate in working groups, method by which they will consider the HANC outputs, and other constructive plans for providing input to these and other network-wide initiatives.

Although letters of commitment/support are not required, applicants may consider providing them to demonstrate the support of consortium participants and collaborators such as Senior/Key Personnel and Other Significant Contributors included in the grant application. When considering who submits letters of commitment/support, applicants should remember that superfluous materials reduce the time reviewers can invest in evaluating the application and can decrease the potential pool of qualified reviewers due to conflicts of interest. Do not place letters of commitment/support in the Appendix section of the application. Letters of commitment/support are to be attached as PDFs to Section 14 of the Research Plan section of the PHS 398 and do not count to the page limits of the components in the application.

These examples or some other designation are appropriate as long as each designation is clearly defined and consistently applied, so that reviewers can easily identify what each designation refers to.

For each of the components, applicants must respond to all FOA instructions; therefore, all relevant equipment to support the CTU’s capacity should be listed in the appropriate component section(s) even if this is redundant with the Resources page.  In addition, the PHS 398 Resources page should include a listing of relevant resources available to the grantee at all of the CTU components. It is appropriate for the Resources page to reference additional details for a piece of equipment in the component sections (provide component and page number) to assist the Reviewers in finding the complete information, but it is expected that the Resources page will include a list of all Resources that the applicant would like to highlight in their application.

Some NIAID, NIH staff work closely with grantees as part of their routine grant oversight responsibilities, and it is not necessary to specifically identify those staff in an application. Naming specific NIAID, NIH staff in an application should be reserved for identifying associations that extend beyond regular research grant management/oversight activities. If such associations exist, they should be explained, and the NIAID, NIH staff should be identified in the application. The associations may constitute a conflict that will be managed, pre- and/or post-review, according to NIH/NIAID policy.

Although it is expected that the grantee organization will enter into a written agreement with CRS organizations involved in the science of the project (i.e., performing requirements of an approved protocol), this does not preclude a CRS from entering into other arrangements with individuals who are outside their organization. For example they may need to support consultants to meet the specific need of a protocol. Please refer to the NIH Grants Policy Statement (Section 15: Consortium Agreements) for further information.

The NIH expects that grant applications will be submitted on time. For CTU applications, receipt of the application by the Center for Scientific Review, by January 29, 2013, as noted on the funding announcement is considered on time submission. NIH will not provide permission for a late submission in advance. Refer to NIH Guide Notice NOT-OD-11-035 for further information.

Part I, Section 2.6 of the PHS 398 instructions state that the applications must use standard size (8 ½" x 11") sheets of paper and provide at least one-half inch margins (top, bottom, left, and right) for all pages, including continuation pages. A4 paper is 8.27 x 11.69 inches. Although, applications submitted on A4 paper will not be returned, applicants must ensure margin guidelines as described in PHS 398 are followed in order to facilitate scanning of the application into the system.

No. Since the final determination of successful NLG applicants is still unknown, general letters of support/commitment from current Network Leadership Group awardees are not encouraged.

Since Component 1 "CTU Research overview" is intended to capture the essence of the entire application and is the only component that will be scored individually, it is also the only component that requires this specific PHS 398 mandated review criteria (Significance, Investigator, Innovation, Approach, and Environment). Each of these review criteria will be considered and contribute to the overall score for component 1. Please note that these criteria do not necessarily have to be ordered in the same sequence as described in the FOA, as long as the required elements are easily identified by the reviewers within component 1.

Components 2 through 11 do not include these five specific review criteria. CTU applications should include specific responses to the guidance listed in Section IV as well as the review criteria noted in Section V of the FOA for each component.

The Clinical Research Network Leadership grants for the next cycle will not be awarded by the time the CTU applications are due; therefore, it is unclear how each Network will manage their annual meetings. For planning purposes in the CTU application, it would be appropriate to anticipate that there will be at least one annual network meeting in the Washington, DC, metropolitan area as is the current practice. Network meetings currently range from one to two meetings in the DC metropolitan area, and the meetings usually run for about 4 to 6 days.

There is no minimum requirement for attendance from a CTU, but CTU staff is expected to be fully integrated into the networks with which they participate and the annual meeting is an important forum for network wide discussions, trainings, and other engagements.

Traditionally we have had the CTU PI, CRS Leader, CRS Coordinator, CAB representative, Pharmacist of Record and one or two other individuals from a CRS attend the meeting. Additional staff from the CTU may be required at these and other meetings based on the agenda of issues and/or training sessions planned.

Some flexibility, based on applicant experience and plans, is possible in Component 1. However, since the CTU applications are responding to an RFA, applicants must first adhere to the specific guidance in the CTU FOA. The PHS 398 instructions are to be followed when the CTU FOA guidance refers to them.

Therefore, organize Component 1, "Research Strategy," in no more than 30 pages according to the CTU FOA guidance.

1. First, follow PHS 398 instructions Section5.5.3 inclusive of Significance, Innovation and Approach.
2. Then provide a Table in the CTU FOA-specified  format that identifies the PDs/PIs; CRSs, CRS Leaders, and the CRSs network affiliations.
3. Then, according to the CTU FOA requirements, address "Network Participation" and "Scientific Leadership."

To facilitate its evaluation, Component 1 also should be developed with attention to its Review Criteria, specifically, Significance, Innovation, Approach, Investigator, and Environment  (see CTU FOA Section V. Application Review Information, Scored Review Criteria – Component 1). Areas within Component 1 that address these review criteria should be identified using the appropriate subheading.

However, all the issues called for in Component 1 need not be categorized only into these five areas; additional subheadings are acceptable.

A CTU application is considered a renewal as long as it is being submitted by a currently funded CTU grantee institution which proposes to conduct HIV/AIDS Clinical Research Network activities, even though the composition of the CTU and proposed Network affiliations may be different from the current configuration. Please note that the CTU application title may change and still be considered a renewal, as long as the grantee institution remains the same.

As outlined in Part I, Section 4.6 (Biographical Sketch) of the PHS 398 guidelines, this section must contain the biographical sketches of all individuals listed as Senior/key Personnel and Other Significant Contributors. Therefore, in addition to the CTU FOA identified Key personnel, biosketches are also required for Other Significant Contributors.

The Center for Scientific Review (CSR) will perform black and white (B&W) scans of the applications. However, if some pages with color material are not resolvable in B&W, the Scientific Review Program provides reviewers color versions of those pages.

The six-page limit for component 11 is the total maximum page limit for all CRSs proposing to affiliate w/the Antibacterial Resistance Network.

In addition to the clinical research network evaluation of CRSs, CTUs are expected to be continuously evaluating their component parts and as such, CTU applications must include a description of the process for assessing and improving performance and capacity of all components of the CTU, as well as reporting relevant information to NIAID and the clinical research network leadership group (LG). The CTU evaluation of its components is not expected to replace the clinical research network performance evaluation but rather include it as part of the overall internal CTU evaluation process. In addition, close-out procedures for poorly performing CTU components must also be included in the application. It is expected that the CTU PDs/PIs will work closely with the clinical research network LG and NIAID to provide an opportunity to improve performance for poorly performing components.

All NIH grants are subject to adherence of the terms and conditions of award, as provided in the Notice of Award (NOA). In addition, a CTU that is not performing in accordance with NIAID standards may have their funds discontinued.

An institution must have a valid Federal Wide Assurance (FWA) in order to receive U.S. Department of Health and Human Services support for research involving human subjects. Each FWA must designate at least one IRB registered with OHRP. If the applicant organization does not have an approved FWA on file with OHRP at the time of the application, the signature on the Face Page of the PHS 398 application is a declaration that the applicant organization will comply with 45 CFR Part 46 and proceed to obtain an FWA. NIH funding will not be provided to a CTU applicant without a valid FWA for the institution.

We encourage applicants to seek opportunities for consolidation of activities within the clinical trials unit. The CTU FOA emphasizes coordination of activities, to achieve efficiencies and avoid redundancies, to the extent possible and practical.

When considering CRS disposition within a unit, applicants should consider several factors including CRS Leadership, extent of resources shared, geographic location, institutional affiliation, and scope of IRB authority. It is understandable that some specific activities within a given CRS may be discrete; however, the overall goal should tend towards coordination within a CRS.

Although we do not necessarily expect the CRS Leader to have the breadth of scientific expertise to actively conduct research within the entire spectrum of Network affiliations proposed, it is expected that the overall CRS management will fall under the leadership of a single CRS Leader, and if necessary, some components of the scientific leadership may be delegated to other qualified individuals within the CRS.

The CRSs proposed in applications are expected to have an appropriate infrastructure in place and be capable of initiating participant enrollment upon award. In rare cases, minimal costs may be requested for "minor" alterations, renovations or repairs with adequate justification.

Core funds provide financial support to maintain minimal infrastructure and staff at the CTU irrespective of protocol activity. Core funds do not include expenses directly attributable to the development, approval, or conduct of specific clinical trials. Core funds may include (but are not limited to)

• Salaries for
  • CTU Program Director(s)/Principle Investigator(s) (PD(s)/PI(s)) to maintain CTU administration and an ongoing contribution to clinical research network science
  • Personnel for CTU administration, oversight, and evaluation and may include some support for a CTU Coordinator, financial and administrative staff
  • Regulatory, pharmacy, data management, and laboratory oversight staff
• Community education and engagement structures and activities that are not study specific
• Community Advisory Board (CAB)
• Clinical quality management activities
• Maintenance and replacement of equipment
• Travel for attendance at clinical research network meetings
• Mentoring and staff training activities

Protocol funds (PF) provide additional support to the CTU to cover protocol-related expenses attributable to protocol development, implementation, or close-out of a clinical trial. Protocol funds include, but are not limited to

• Salary for additional staff or expanded commitment of core staff
• Protocol development activities (e.g., translations, printing)
• Participant recruitment and retention
• Protocol required tests and evaluations
• Participant reimbursement
• Equipment and supplies
• Community education and engagement structures and activities that are study specific
• Additional support for regulatory, pharmacy, data management, and laboratory activities to support a specific protocol

Core funding amounts are determined by NIAID based on the size and scope of the CTU.

Protocol funding amounts are recommended by the NIAID clinical research network Leadership Groups based on specific study requirements.

An awardee is expected to rebudget existing funds to meet legitimate needs. However, in rare circumstances, PF may be restricted in a Notice of Award (NOA) to be used only for the purpose stated in the restriction.

NIH expects our grantees to follow existing U.S. policies and regulations concerning management and accounting. The NIH Grants Policy Statement (http://grants1.nih.gov/grants/policy/nihgps_2010/index.htm) is an excellent resource for all NIH policies and regulations for recipients of NIH grant awards.

Each institution where a CRS is located is required to have an FWA. Therefore, two CRSs affiliated with the same institution can share one FWA. Further information on FWA policies can be found at the Office of Human Research Protection website: http://www.hhs.gov/ohrp/.

Each institution where a CRS is located is required to have an FWA. It is also required to designate an IRB, whose role is to approve and periodically review the research being conducted at that CRS to ensure the adequate protection of human subjects. This IRB must be named in the FWA of the institution where the research will be performed. Multiple CRSs located at the same institution may function under the same FWA. They may or may not have the same IRB. Please see the Office of Human Research Protections for more information.