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

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

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

The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications from domestic and foreign institutions to serve as Clinical Trials Units (CTUs) for NIH HIV/AIDS Clinical Trials Networks. The CTUs will participate in the development of trials, coordinate and execute clinical trials, provide clinical sites, local laboratory capacity, and pharmacy support.

The National Institute of Allergy and Infectious Diseases (NIAID) and its IC partners currently support five HIV/AIDS clinical trials networks: the AIDS Clinical Trials Group (ACTG), the HIV Prevention Trials Network (HPTN), the HIV Vaccine Trials Network (HVTN), the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT), and the Microbicide Trials Network (MTN). NIAID is soliciting applications for FY21 award consideration for the following four HIV/AIDS Clinical Trials Networks: HIV Prevention Clinical Trials Network, HIV Vaccines Clinical Trials Network, HIV/AIDS Adult Therapeutics Clinical Trials Network, HIV/AIDS Maternal, Adolescent and Pediatric Therapeutics Clinical Trials Network.

Since the beginning of the HIV/AIDS pandemic, the National Institutes of Health (NIH) has advanced understanding of disease mechanisms and used basic science to create opportunities for the discovery, development, and clinical evaluation of novel prevention and treatment strategies. With this approach, the scientific community has created an array of effective tools to treat and prevent HIV infection. Over the last 35 years, these interventions have been made safer and more effective. However, according to the latest Joint United Nations Programme on HIV/AIDS (UNAIDS) Global summary of the AIDS epidemic, there are approximately 36.9 million people living with HIV, 25.7 million of whom are living in sub-Saharan Africa, with 1.8 million new infections per year across the world. Significant challenges remain in delivering treatments and methods of prevention to the people who need them most. Although rates of death due to HIV/AIDS and rates of new HIV infections are declining in many areas of the world, these declines vary by region and in many places are slower than anticipated in reaching 2020 goals. In many parts of the world with generalized HIV/AIDS epidemics, new HIV infections far outpace access to effective antiretroviral treatment (ART). Even in the U.S. and other industrialized nations, where the HIV epidemic continues unabated particularly in most at-risk populations, a large portion of individuals who meet treatment guidelines do not have access to ART.

NIH-sponsored research has led to critical advances in the science beyond what could have been imagined in the early days of the pandemic, developing safe and effective anti-HIV treatments that require only one pill a day, discovering pre-exposure prophylaxis to prevent HIV infection, virtually eliminating perinatal and breastfeeding HIV transmission, developing long-acting technologies for HIV prevention and treatment, and investigating sex-specific methods of HIV prevention.

During the period since the previous competitive renewal for the Clinical Trials Networks, the approach to global HIV prevention has been marked by dramatic change. The ambitious scale-up of treatment and new options for prevention have transformed the HIV landscape both for those at risk of acquiring the disease and for researchers investigating new ways to prevent HIV infection.

Researchers from the CTUs and associated Clinical Research Sites (CRS) have supported the development of NIH-funded HIV/AIDS Clinical Trials Networks and their diverse research priority areas. The success of the networks has relied heavily on the scientific expertise and leadership contributions of the CTUs and associated CRS personnel.

The NIAID currently supports 37 CTUs comprised of approximately 100 CRSs worldwide. Each CTU participates in one to five of the existing HIV/AIDS Clinical Trials Networks, and collectively have enrolled over 86,000 participants in Phase I, Phase II, Phase IIb, and Phase III observational and interventional studies through January 2019. The CRS distribution has been predominantly reflective of the communities most heavily impacted by the HIV/AIDS epidemic.

NIAID is soliciting applications for FY21 award consideration for the following HIV/AIDS Clinical Trials Networks:

• RFA AI-19-003: HIV/AIDS Adult Therapeutics Clinical Trials Network
• RFA AI-19-004: HIV/AIDS Maternal, Adolescent and Pediatric Therapeutics Clinical Trials Network
• RFA AI-19-005: HIV Prevention Clinical Trials Network
• RFA AI-19-006: HIV Vaccines Clinical Trials Network

Research Priority Areas for each of the HIV/AIDS Clinical Trials Networks can be found on the NIAID website here.

In addition to continuing to provide the scientific expertise and clinical research infrastructure to conduct NIH HIV/AIDS clinical protocols, CTUs may participate in the development of strategies, interventions and products against other diseases (not listed in the stated research priority areas) and to implement clinical trials in support of those areas as appropriate. The research agenda for those efforts will be developed post-award through cross-network, joint leadership efforts in conjunction with NIAID and other NIH staff.

Each HIV/AIDS Clinical Trials Network is composed collectively of a Leadership and Operations Center (LOC), Laboratory Center (LC), Statistics and Data Management Center (SDMC) and affiliated Clinical Trials Units (CTUs) and Clinical Research Sites (CRSs). Each will be funded via an independently-solicited FOA and each will contribute specific essential functions necessary to support a large-scale, complex clinical research program. While the emphasis of each network is clinical trials, clinical research studies that aren't NIH-defined clinical trials are also in scope when needed to support the program. For the purpose of this FOA, the term "clinical study" refers to both clinical trials and clinical research studies, and "clinical trial" is used to refer to clinical trials only.

The LOC will manage the network’s scientific priorities and the corresponding alignment of clinical studies with those priorities. The LOC has primary responsibility for the prioritization, selection and development of clinical protocols and project management of the full spectrum of activities needed to plan and conduct clinical trials including the coordination of efforts by the LC and SDMC, and clinical sites. The LOC has responsibility to assure that the research is conducted according to principles of Good Clinical Practice (GCP).

The LC will lead the development, implementation and evaluation of the laboratory activities that are required to carry out the network research agenda. The LC will ensure that there are relevant state-of-the-art expertise and technologies to provide clinically useful study data and enable sound product development decisions. The LC will oversee laboratory operations that allow for consistent and reproducible laboratory results that can support study reconstruction.

The SDMC will provide comprehensive data management and data analyses for network clinical studies in compliance with regulatory standards. The SDMC will provide leadership and services for biostatistics, study design, analysis, interpretation and publication of results, including innovative statistical methods, along with state-of-the-art clinical trial management and laboratory information management systems to ensure complete, high-quality data.

The CTUs will provide scientific and administrative expertise as well as the infrastructure to conduct clinical studies within the network. A CTU is composed of at least one, but no more than eight, Clinical Research Site(s) (CRSs) that can contribute to at least two HIV/AIDS Clinical Trials Networks.

Each Clinical Trials Network will have an Executive Management Committee (EMC) to coordinate the activities of the Network's LOC, LC and SDMC. The EMC will include the PDs/PIs from the LOC, LC and SDMC and will be chaired by the PDs/PIs from the LOC.

Additional Resources provided by NIAID:

• Division of AIDS (DAIDS) Clinical Laboratory Oversight Team (DCLOT) helps develop, evaluate, coordinate, communicate, and oversee, the implementation of harmonized DAIDS clinical lab-related guidelines, standards, and requirements. DCLOT members serve as points-of-contact to the LCs, as well as oversee DAIDS-funded contractual laboratory quality assurance resources. These contract resources ensure that network laboratories demonstrate assay proficiency and perform laboratory operations according to good clinical laboratory practices (GCLP). These contracts include:
• Clinical Research Support Services (CRSS),
• Clinical Pharmacology Quality Assurance Program,
• External Quality Assurance Program Oversight Laboratory (EQAPOL),
• Immunology Quality Assurance (IQA) Program,
• Mycobacterium tuberculosis (Mtb) Quality Assessment Program (TBQA),
• Patient Safety Monitoring in International Laboratories (SMILE), and
• Virology Quality Assurance (VQA) Program
• Safety Oversight Committees: NIAID oversees the safety of all participants in clinical trials funded by NIAID. Generally, NIAID DAIDS will provide NIAID-convened Data and Safety Monitoring Boards (DSMBs) to monitor Phase I, Phase II, Phase III and Phase IV multicenter, randomized clinical trials.
• Other Support Services: NIAID will provide additional support services for network trials that must be conducted under an Investigational New Drug (IND) or Investigational Device Exemption (IDE). These services may include domestic and international regulatory sponsorship, management of clinical agents, and clinical site monitoring. In addition, there are NIAID contract resources for clinical laboratory quality assurance and proficiency testing. A detailed description of these resources can be found at this website.

The CTU is a critical component of the HIV/AIDS Clinical Trials Networks. The CTU is structured to reflect a cohesive, integrated unit with demonstrated capacity to participate in the breadth of studies developed by the networks. A CTU is responsible for the coordination and execution of clinical trials under its purview in accordance with the networks, NIAID and other applicable policies. The CTU is composed of multiple elements, including:

• CTU Administrative and Financial Management
• Community
• Site Pharmacy(ies)
• Site Laboratory(ies)
• Regulatory Assurance, Data Management and Training
• Quality Management
• At least one, but no more than eight (8) experienced domestic or international clinical research site(s) (CRS(s))

The CTU provides the scientific and administrative expertise as well as the infrastructure to participate in two or more NIH HIV/AIDS Clinical Trials Networks. Each CTU must demonstrate sufficient breadth and depth of scientific expertise to contribute to the ongoing refinement of the clinical trials network(s) agenda (i.e., the research priority areas of the network(s) as described in the companion FOAs), participate in an array of clinical studies, demonstrate a productive partnership with the community(ies) in which they propose to conduct research, promote efficient utilization of resources and infrastructure, and include continuous performance evaluation and interventions to drive compliance.

The CRS is the center of clinical research activity, defined as a discrete location (e.g., hospital, outpatient clinic, community health center, private practice, local health department clinic) with appropriate, identified and characterized potential trial participants (e.g., demographics, incidence and prevalence of HIV/AIDS) where participant recruitment and retention, protocol management and other clinical research activities are conducted. The CTU will assume the network affiliations of its CRSs.

A priority is placed on reaching populations severely impacted by the HIV/AIDS epidemic whose participation will help address priorities for NIH HIV/AIDS research. These populations include, but are not limited to women, adolescents, sexual and gender as well as other minorities, people who inject drugs in the United States, and populations in low and middle-income countries. CTUs must demonstrate how each clinical research site plans to reach key populations that are impacted by HIV in their catchment area. CTUs with the flexibility and capability to participate in the development and conduct of several clinical research projects in multiple NIAID Clinical Trials Networks and respond to rapidly evolving research opportunities are particularly sought.

A CTU configuration will support participation in at least two clinical trials networks, promote efficient utilization of resources and infrastructure, and include continuous performance evaluation and interventions to drive compliance.

The proposed CTU must demonstrate that there is current sufficient space (facility), dedicated, trained and qualified staff, capacity and institutional commitment to ensure organizational stability to fulfill the CTU’s objectives. The CTU composition including the location of the CTU administrative office, location of CRS(s), number of CRS(s), scope and complexity must be commensurate with the scientific breadth of the clinical trials networks with which the CTU proposes to affiliate.

The CTU and all of its elements (CRSs, laboratories, and pharmacies) must operate in compliance with all applicable regulatory requirements, including the Food and Drug Administration (FDA), International Conference on Harmonization (ICH) GCP, NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements as well as national and local regulatory authorities.

An appropriate staffing plan for the CTU, its CRSs and other elements of the CTU structure is critical to a well-functioning organization that can effectively coordinate and execute clinical trials in the targeted scientific areas. The NIAID has determined that certain positions are crucial for optimal performance and rigorous protocol implementation. For example, individuals with leadership and management expertise are needed to keep projects on time, juggle multiple complex tasks, oversee performance, and ensure adequate staff training. Other individuals are needed with experience in clinical trial implementation, financial management, regulatory compliance, broad supervision and relevant scientific expertise in areas of focus. Finally, some individuals such as the Pharmacist of Record, with highly specialized skills, are also required.

Each CTU will consider the following individuals as 'Senior/Key Personnel':

• A CTU PD/PI who will be responsible for the overall management of the CTU award and may also serve as the primary scientific and administrative representative(s) to the clinical trials network(s).
• A CTU Coordinator who will be responsible for coordination and facilitation of activities across the CTU that may include administration, financial management, training, staff supervision, evaluation, and logistics.
• A designated CRS Leader at each CRS who will oversee the scientific operations within the research priority areas for which the CRS is proposing to affiliate.
• A designated CRS Coordinator at each CRS who will assist in the oversight of all day-to-day activities at an individual CRS.
• A licensed/registered Pharmacist of Record (PoR) who performs the day-to-day pharmacy activities and study product management including, but not limited to, procurement, storage, preparation, dispensing and final disposition of study products for the DAIDS funded and/or sponsored clinical trial(s).

The CTU will be responsible for the following:

Administrative and Financial Resource Management

The CTU Administrative Office serves as the administrative and management oversight location for multiple functions across the CTU areas of responsibilities. The CTU provides oversight for the following clinical-related activities: coordination with the affiliated Clinical Trials Networks, staff training, adherence to regulatory compliance and process development to conduct internal quality control and quality assurance consistent with NIAID clinical research and regulatory policies. The CTU administration develops and coordinates multiple processes to monitor activities, budgets, timelines, and develops strong bi-directional communications practices among all participant locations, sites and functions, including CRS(s), and local laboratory and pharmacy functions. In addition, the leadership of the Administrative section coordinates with NIAID to ensure integration of NIAID-supported resources and services (e.g., safety monitoring, statistical and data management, etc.) into all CTU program elements, as required. The CTU will be led by an experienced CTU leader (PDs/PIs) or leadership team (including the PDs/PIs). Leadership experience is essential to the success of the CTU in implementing high-priority research of the networks and the coordination with the LOCs, LCs, and SDMC.

Community

The CTU will engage in a productive partnership in the communities in which clinical research will be conducted that is consistent with Good Participatory Practice (GPP) guidelines. Each CTU must have a Community Advisory Board (CAB). A CAB is an active group of individuals representing the local population(s) impacted by or at risk of acquiring HIV. The organization and composition of each CAB should reflect local community representation, promote community engagement, and provide local perspective(s) on the implementation of the NIAID clinical research plan(s).

The CTU will be responsible for determining how best to organize community partnerships to meet the research needs and priorities of the local population in a collaborative and transparent manner. A CTU may include multiple CABs if required to enable effective representation of the populations involved, for example, to represent geographically, culturally, or other distinct populations.

Pharmacy

Each CRS must have access to a secure pharmacy facility staffed by qualified pharmacist(s) in order to receive, store, manage inventory, dispense study product, and maintain accurate records in accordance with FDA/ICH GCP, applicable United States regulations, NIAID guidelines and local requirements/regulations. The CTUs may elect to utilize appropriate pharmacy services, such as a research pharmacy operated by a medical facility or provide independent pharmacy services within the CTU. When practical and efficient, CTUs may utilize a single pharmacy to support multiple CRSs. The Pharmacist(s) of Record (PoR) is/are responsible for overseeing all pharmacy-related activities. Pharmacies will use secure internet connections to access the Online Site Management and Ordering System for study products via web browser. Pharmacies will use secure connections to interact with the SDMC.

Laboratory

Under the leadership of each Network Laboratory Center (LC), CTU/CRS laboratories conduct activities required to carry out the clinical research network agenda. Each CRS must have access to an accredited Clinical Laboratory Improvement Amendment (CLIA), or other Good Clinical Laboratory Practice (GCLP) compliant local laboratory capable of protocol-specified testing, specimen processing, laboratory data management capabilities, and shipment and storage of samples collected at the CRS. Laboratories must meet and maintain specific requirements to ensure compliance with GCLP and other DAIDS-supported laboratory requirements. Laboratories must have the ability to ship specimens out of the country and execute Material Transfer Agreements, in compliance with all local, domestic, and international regulations, as necessary. The CTUs may propose to utilize as appropriate, local laboratory services such as hospital clinical pathology departments and commercial laboratories or provide independent laboratory services within the CTU. When practical and efficient, CTUs are encouraged to utilize a single laboratory to support multiple CRSs.

CTU laboratories work closely with the Network Laboratory Center (LC) to carry out the clinical research network agenda. The local laboratory is expected to be responsive to the LC, SDMC, DAIDS and the DAIDS-funded Laboratory QA contractors. Secure information technology is required to utilize the laboratory information management system provided through the Network SDMC and coordinated by the LC and the clinical trial management system provided by the SDMC.

Laboratories will use validated systems and secure internet connections to access Network resources and SDMC-supported clinical trial management systems.

Laboratories will participate in proficiency testing programs provided by NIAID DAIDS contract support. Laboratories will be subject to GCLP audits and clinical monitoring by third-party monitors and inspection by regulatory agencies.

Regulatory Assurance, Data Management and Training

• Regulatory Assurance: Each CTU and CRS must have an efficient process to ensure compliance with all applicable regulatory requirements, including FDA/ICH GCP, NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements as well as national and local regulatory authorities. The CTU and its elements must maintain a state of regulatory agency inspection readiness at all times.
• Data Management: The CTU and each CRS must be capable of effectively and efficiently communicating with the SDMC, LC, and LOC. Each CRS must have a robust system to collect, manage, and report clinical research data in accordance with FDA/ICH GCP, Good Documentation Practices (GDP), NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements as well as national and local regulatory authorities. Electronic systems to collect, manage, and report clinical research data must be validated in accordance with FDA/ICH GCP requirements. CRSs are encouraged to support direct data entry.
• Staff Training: Each CTU and CRS must have adequately trained and experienced personnel to conduct all required clinical research activities. In addition, each CTU/CRS must have a process for ongoing assessment and delivery of training to ensure staff have the appropriate knowledge and qualifications to conduct clinical research in compliance with protocol requirements, FDA/ICH, GCP, GDP, DAIDS clinical research policies, Country-specific regulations, and clinical trials network requirements.

Quality Management

The purpose of Quality Management is to ensure protocol regulatory compliance, ensure human subjects protection and data integrity, and compliance with all applicable regulatory requirements. Each CTU will have a Clinical Quality Management Plan (CQMP), which describes a Quality Management (QM) system that is used to direct, control and manage quality for clinical trials of each CRS including local laboratory and pharmacy. QM systems include defined quality requirements as well as site procedures, forms and templates, quality control (QC) and quality assurance (QA) processes, corrective and preventive action (CAPA) processes and continuous quality improvement activities that support data completeness and data integrity.

Each CQMP must comply with the DAIDS "Requirements for Clinical Quality Management Plans" Policy found here. Each CQMP will include an evaluation of periodic Quality Control and Quality Assurance activities and a process for continuous quality improvement plans, that may require changes to site practices and the CQMP as necessary.

Clinical Research Site(s) (CRS)

A Clinical Research Site serves as a location where clinical studies are conducted. The CRS will provide the necessary participants, facilities and infrastructure required to implement the affiliated network research. Each CRS has a designated CRS Leader qualified to oversee the scientific operations within the research priority areas for which the CRS is proposing to affiliate. The CRS leadership will monitor compliance with FDA/ICH, GCP, local regulatory and other requirements at the CRS level. CRS leadership will work closely with the CTU leadership and other staff to assess current and future capacity at the CRS, project protocol commitments, resources and costs.

Each CTU consists of at least one but no more than eight Clinical Research Sites. Applications proposing more than eight CRSs will not be responsive, and therefore not reviewed.

The CRS must be fully equipped and staffed by qualified professionals capable of conducting clinical research for one or more clinical trials networks in accordance with Good Clinical Practice (GCP), national and local regulatory requirements, and other applicable NIH requirements.

The number of CRSs at any one institutional location (e.g., hospital or medical campus) should be limited to the number required to provide appropriate and cost-effective clinical research oversight for diverse populations (e.g., pediatrics, adult medicine). However, it is expected that each institutional location will have no more than one CRS for each of the diverse populations. Where practical and efficient, applicants are encouraged to combine the operations of diverse populations into one CRS.

Each CRS will support between one and four Networks. Each CRS will have access to potential clinical study participants (e.g., demographics, incidence and prevalence of HIV/AIDS) to support each Network proposed and each CRS will have established community engagement activities. Each CRS may be proposed in only one CTU application.

Protocol-Specific Sites

In addition to the CRSs listed in the application, there may be limited future opportunities to bring on protocol-specific (PS) sites to meet HIV/AIDS Clinical Trials Network needs or NIAID priority emerging infectious disease research agendas during the project period. These PS sites will be identified by the clinical trials network, CTU, or NIAID to meet a discrete need and must be approved by NIAID. For example, a PS site may be considered to accomplish protocol-specific recruitment goals, if the capacity does not exist at currently-funded CRSs. These PS sites will be scheduled to close, and funding discontinued, upon completion of the specified protocol activities. It is expected that these protocol-specific sites will be affiliated with CTUs.

Protocol-specific sites should not be named in this application. Protocol-specific sites will be identified and proposed after award, based on identified protocol-specific clinical trials network needs. PS sites will be trained on protocol process through the Network as part of protocol activation.

External Interactions and Opportunities. The CTUs will be strongly encouraged to collaborate with other NIH-supported networks and other Federal and private sector clinical research programs, and to interact with government, non-government and community organizations (including the private and non-profit sector), to effectively develop and implement a clinically relevant, comprehensive, interdisciplinary and cost-efficient research agenda. Such a collaborative research agenda should utilize the strengths, experience and expertise of the various collaborating organizations. The sharing of expertise, resources and procedures is expected in key areas, including: development of clinical infrastructure in resource-limited settings; harmonization of laboratory resources and specimen management; harmonization of common data elements and data entry interfaces; community engagement, including development, training and support of community advisory boards. The CTU is expected to support maximal use of the specimens collected during the course of NIH-supported clinical studies.

Funding to carry out the network’s clinical research agendas falls into two categories:

Core Funds. NIAID will provide core funds directly to the CTUs annually to support the CTU functions, including CRSs. Core funding is the initial fixed-base funding and provides infrastructure and salary support that is not protocol-specific. CTU core funds will be determined by NIAID based upon the size and scope of the funded CTU.

Core funds include (but are not limited to) baseline support for the following activities:

• Personnel salary to:
• maintain CTU and CRS administration
• facilitate oversight and evaluation of CTU elements
• support an ongoing contribution to clinical research network science
• provide support for regulatory, pharmacy, data management, and laboratory staff
• Community education and engagement structures and activities
• Communicating study results to participants and the community
• Clinical quality management activities
• Maintenance and replacement of equipment
• Travel to attend clinical trials network meetings
• Mentoring and training of staff
• Record retention to meet regulatory requirements

While core funding will be supported by NIAID, applicants should keep in mind that the funding instrument is a 'grant in aid', and therefore may not cover 100% of these expenses. Applicants are encouraged to develop collaborations to enhance utilization of existing resources.

Protocol Funds (PF). NIAID will provide PF to support the implementation of network protocols, including protocol-specific infrastructure or other requirements needed to conduct protocols at a site. PF varies annually, depending on costs of ongoing protocols and will be awarded 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) the following protocol-specific expenses:

• Personnel salary to support protocol activities
• Protocol specific regulatory activities
• Participant recruitment and retention
• Protocol required tests and evaluations
• Participant reimbursement
• Travel for protocol-specific personnel, as required by Network, to attend clinical trials network meetings
• Travel to attend protocol-specific trainings
• Equipment and supplies
• Community education and engagement structures and activities
• Communicating study results to participants and the community
• Protocol specimen shipment and storage

NIAID expects that equipment and services funded via Core or PF will be made available, as appropriate, for other NIAID-funded network activities regardless of how funds were initially provided to purchase those items.

Based on communications with the LC, SDMC and CTUs/CRSs, the LOC will estimate protocol funding needs for the network (salary and non-salary PF) annually and submit a budget request to NIAID. NIAID will then determine the amount of PF to be provided in the coming grant year. Adjustments in PF allocation will be made at regular intervals during each budget period, based on both performance and availability of funds.

Distribution of Protocol Funds to Network-Affiliated CTUs/CRSs

NIAID anticipates providing PF salary support directly to network-affiliated CTUs and adjusting PF allocation mid-budget period based on both performance and availability of funds. CTUs/CRSs will receive non-salary PF support through the associated network LOC. In rare circumstances re-budgeting between core and PF is allowable to meet unanticipated costs. Similarly, in rare circumstances when additional funds are needed and NIAID funds available, NIAID may negotiate time limited administrative supplements.

Note: For further information please visit the following website for general information and questions and answers.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

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
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

An individual may be listed as PD/PI (or as part of a multi-PD/PI team) on only one CTU application.

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

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

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

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

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, 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 activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Robert Unfer, Ph.D.
Telephone: 240-669-5035
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following additional instructions:

The Research Strategy must consist of the following sub-sections with the indicated page limits:

Sub-section A. Overview of the Clinical Trials Unit (CTU) - one required - 30 pages

Sub-section B. Administrative and Financial Resource Management - one required - 6 pages

Sub-section C. Communication - one required - 6 pages

Sub-section D. CTU Evaluation - one required - 6 pages

Sub-section E. Community - one required - 12 pages

Sub-section F. Pharmacy - one required - 12 pages

Sub-section G. Laboratory - one required - 12 pages

Sub-section H. Data Management - one required - 6 pages

Sub-section I. Regulatory Assurance - one required - 6 pages

Sub-section J. Training and Mentoring - one required - 6 pages

Sub-section K. Quality Management - one required - 12 pages

Sub-section L. Clinical Research Site(s) (CRS) - one required, maximum of eight - 12 pages each

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

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

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

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

Facilities & Other Resources: Applicants must provide information related to the facilities and other resources available to the CTU to implement the network research agenda(s). For the CTU, follow the instructions in the SF424 Applicant Guide to complete this section.

In addition, for each proposed CRS, in a clearly marked sub-section starting with CRS 1 (name or name/NIAID Clinical Research Management System [CRMS] site ID, if applicable) to CRS 8 (name or name/NIAID CRMS site ID, as applicable), include the information requested below. All information should be provided into a single PDF file for upload.

Facility: Describe (i) the clinic facilities including location, layout, equipment, vehicles, security and other key infrastructure required for efficient, uninterrupted clinical research; (ii) any specialized capabilities available in the location(s); and (iii) the IT infrastructure, including computer and internet connectivity and bandwidth that supports adequate security.

Pharmacy: Describe (i) the pharmacy facilities including location, infrastructure, equipment (e.g. refrigerators, freezers, temperature monitoring system, power generator(s)), other specialized equipment, storage, systems for security, inventory or other key processes; (ii) and identify which CRSs the pharmacy facilities will support; (iii) any specialized capabilities available in the pharmacy locations(s). Describe pharmacy facilities and equipment with respect to compliance with quality standards as described in USP Chapters <795>, <797>, and <800> or their equivalent (e.g., compliance with ISO class 5 environment standards, etc.). If a CRS does not have a local Pharmacy facility, identify which Pharmacy location will support the CRS described and provide the requested information about the pharmacy.

Laboratory: Describe (i) the laboratory facilities including location, infrastructure, equipment (e.g., hematology analyzer, power generator(s)), other specialized equipment, storage, systems for security, inventory or other key processes; and (ii) any specialized capabilities available in the laboratory locations(s).

Describe the extent to which the local laboratory has testing capacity for each of the following tests. If a CRS does not have a local Laboratory facility, identify which Laboratory location will support the CRS described.

• Chemistry
• Histology
• Toxicology
• Hematology
• Immunology
• CD4
• Immunology/Serology
• Virology/HIV Viral Load/HIV DNA or Total Nucleic Acid/HIV Resistance Genotyping
• Metabolic Tests
• Microbiology
• Pharmacology
• Cytology
• Specimen Processing
• TB
• Urinalysis

Other Attachments: Applicants must provide the following additional material specified below. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks).

Attachment 1. Proposed Clinical Trials Network Affiliation per CRS (use filename "Overall CRS-Network")

Each CRS must propose to affiliate with at least one HIV/AIDS clinical trials network. Provide the following information in a table format for each CRS (if desired, applicants may use the suggested Overall CRS-Network Table format described at the following website): CRS Name, current NIAID CRMS site ID (if applicable), CRS Leader, Network Affiliation (HIV Vaccines Clinical Trials Network, HIV Prevention Clinical Trials Network, HIV/AIDS Adult Therapeutics Clinical Trials Network, and/or HIV/AIDS Maternal, Adolescent and Pediatric Therapeutics Clinical Trials Network)

Attachment 2. CRS Site Characteristics (use filename "CRS Site Characteristics")

For each proposed CRS, provide the following information in a table format to describe the participant cohort(s) that the CRS has demonstrated experience recruiting into clinical trials. For each CRS provide the following categories and population characteristics (if desired, applicants may use the suggested Site Characteristic table format described at the following website) labeled by site name and site number (if applicable). Include the following categories and population characteristics:

• Sex: Female, Male, and/or Transgender
• Age: Infant, Children, Adolescent (13-17 years), Young Adult (18-24 years), and/or Adult
• Race: American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, White, and/or Other Race
• Ethnicity: Hispanic or Latino and/or, Not Hispanic or Latino
• Risk Factor: Mother-to-Child Transmission (MTCT), Men Who Have Sex with Men (MSM), Bisexual, Heterosexual, Sex Work, Transactional Sex, People Who Inject Drugs, Sero-Discordant Couple, Breastfeeding/Lactating, and/or Substance Abuse
• Disease/Condition: HIV Uninfected, HIV Exposed Infants, HIV Infected, HIV Clade A, HIV Clade B, HIV Clade C, HIV Clade D, HIV Clade E, Acute HIV Infection, Chronic HIV Infection, Treatment Na ve, HIV Related Malignancies, HIV/TB Co-infection, TB, MDR TB, XDR TB, HIV/HBV Co-Infection, HBV, HIV/HCV Co-infection, HCV, Infectious Comorbidities, Non-Infectious Comorbidities, Pregnancy, and/or Post-Menopausal

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

Applicants will designate specific roles to staff the CTU in a manner sufficient for optimal performance for the administrative, management and scientific aspects needed to conduct clinical research and clinical trials. Each CTU must designate individuals in the following roles as 'Senior/Key Personnel': CTU PD(s)/PI(s), CTU Coordinator, CRS Leader(s), CRS Coordinator(s), and Pharmacist(s) of Record.

• In the biosketch describe the relevant experience of the CTU PD(s)/PI(s) in leading and managing a complex HIV/AIDS clinical research operation including the roles and responsibilities served. Describe experience providing oversight and management of IND-level protocols conducted at multiple clinical research sites, including scientific contributions, strategic planning, prioritization, and resource allocation within a highly regulated research environment.
• In the biosketch describe the relevant experience of the CTU Coordinator that demonstrates administrative and financial management, training, staff supervision, evaluation and logistics of a complex clinical research operation within a highly regulated research environment commensurate with the size and scope of the proposed CTU structure including the roles and responsibilities served. Describe relevant experience conducting and driving compliance across multiple, complex, IND-level clinical research protocols.
• In the biosketch describe the relevant experience of the CRS Leader for each proposed CRS that demonstrates significant experience conducting and driving compliance across multiple, complex, IND-level HIV/AIDS clinical research protocols including the roles and responsibilities served. Describe experience with training, staff supervision, evaluation and logistics of a complex clinical research operation commensurate with the size and scope of the proposed CRS.
• In the biosketch, describe the relevant experience of the CRS Coordinator for each proposed CRS that demonstrates relevant experience conducting complex, IND-level clinical research protocols including the roles and responsibilities served.
• In the biosketch, describe the relevant experience of the Pharmacist(s) of Record (PoR) for each proposed CRS that demonstrates relevant experience providing pharmaceutical support and oversight for a clinical research operation conducting IND-level protocols within a highly regulated research environment including the roles and responsibilities served.

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

The applicant should request only Core funding. Core funding is the initial fixed-base funding and provides infrastructure and salary support that is not protocol-specific. Examples include, but are not limited to:

• Administrative and management support
• Community education and engagement structures and activities
• Communication of study results to participants and the community
• Clinical quality management activities
• Maintenance and replacement of equipment
• Travel to attend HIV/AIDS Clinical Trials Network meetings
• Mentoring and training of staff
• Record retention to meet regulatory requirements

The proposed budget may include infrastructure expenses such as personnel salary, travel to network meetings for appropriate clinic, laboratory and pharmacy staff, general supplies, equipment and record storage at the CTU and proposed CRSs.

Considering the overall CTU budget, CTUs shall provide support, including but not limited to reasonable costs for CAB or other stakeholder meetings and associated expenses. CTUs will also be expected to provide reasonable accommodation, access to trainings, local engagement activities and other means of educating and/or engaging the CAB and community stakeholders at large.

Protocol Funds (PF) should not be requested; PF will be determined and provided as protocols are initiated through a collaborative process between the NIAID and awardees.

Applicants proposing multiple PD(s)/PI(s) should include information describing how the proposed effort of each individual is commensurate with the size and scope of the CTU.

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

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

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

Specific Aims: Describe the specific aims of the proposed Clinical Trials Unit (CTU).

Research Strategy: The research strategy must consist of sub-sections A-L as designated below.

Sub-section A. Overview of the Clinical Trials Unit

Organizational Structure: (i) Provide an organizational chart describing the overall CTU structure that demonstrates a cohesive, synergistic, integrated approach to supporting the NIH HIV/AIDS clinical trials networks for which the CTU is proposing to affiliate; include a detailed description of lines of authority; (ii) Describe plans for a staffing structure, with roles and responsibilities that capitalize on the specific strengths of the CTU PD(s)/PI(s), CTU Coordinator, CRS Leader(s), CRS Coordinator(s) and Pharmacist(s) of Record; (iii) Describe prior relationship(s) between CTU elements and summarize outcomes, and/or planned collaborations and anticipated value; and (iv) address any innovations unique to their organizational structure or processes to facilitate optimal performance to manage, conduct and evaluate clinical research protocol activities at CRSs.

Network Affiliations: Provide detailed justification for the proposed affiliation with the Networks and corresponding Network research priority areas.

Institutional Commitment/Support: Describe (i) the available administrative positions to support the CTU; (ii) strategies to defray the total costs of CTU operations; and (iii) institutional resources, including funds if any, under the control of or otherwise accessible to the PD(s)/PI(s) for the CTU to ensure adequate staffing and resources.

Performance and Past Experience: Describe (i) performance over the previous 5 to 7 years with participation in IND-level or other complex HIV/AIDS multicenter clinical trials or equivalent experience; (ii) strengths in overseeing and managing a complex clinical trials enterprise; and (iii) challenges experienced in overseeing and managing a complex clinical trials enterprise, as well as activities undertaken to overcome those challenges.

Scientific Leadership and Governance: Describe (i) the scientific leadership structure within the CTU; (ii) the proposed points of integration with the NIH HIV/AIDS clinical trials networks. Summarize the proposed approach to making high-level scientific decisions including selection of protocols in which to participate, as well as reassessment and redirection of resources to support the scientific priorities of the proposed networks; and (iii) plans for CTU and CRS staff to contribute to the development of the network clinical research plans through activities such as membership on protocol teams, scientific and resource committees, and review of proposed concepts and protocols.

Scientific Leadership Diversity: Briefly describe how diversity is promoted and encouraged within the CTU/CRS scientific leadership to reflect the diversity of the populations from which participants are recruited.

For renewal applications: Progress Reports should be included.

Sub-section B. Administrative and Financial Resource Management

Describe (i) approaches to efficient utilization of resources and infrastructure, avoidance of redundancies, resource sharing strategies, and cost containment measures across the CTU; (ii) the financial management structure, including plans for an appropriate staffing structure with roles and responsibilities; (iii) policies and procedures for establishment and implementation of sub-contract agreements, including timelines and responsible parties; (iv) policies and procedures for monitoring and adjusting resource utilization; (v) the process for allocating resources to each CRS in a transparent manner; and (vi) the plan to provide timely financial status information to the LOC and NIAID, including all funding sources to the CRSs.

Sub-section C. Communication

Describe (i) how the CTU will establish and maintain clear lines of communication within the CTU related to day-to-day operations, including how decisions will be communicated and dissemination of relevant information in a timely manner; (ii) how the CTU will establish and maintain clear lines of communication between the CTU and other components of the Network (LOC, LC, and SDMC); and (iii) communication plans between the CTU and NIAID DAIDS staff (do not include specific NIAID staff names in the application); and (iv) Describe the process for communicating study results to study staff, participants, and the community as soon as possible after protocol unblinding or after receipt of the results summary from the LOC.

Sub-section D. CTU Evaluation

Describe (i) the process for assessing and communicating capacity of all elements of the CTU prior to conducting each protocol to ensure compliance with FDA/ICH GCP, NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements, as well as national and local regulatory requirements; (ii) how the CTU will prepare the CRS(s) for protocol implementation including responsible parties; (iii) the active, ongoing process, including metrics and frequency, for assessing operational performance of all elements of the CTU and reporting relevant information to the NIAID and the clinical trials network; (iv) how improvements in performance across all elements of the CTU will be achieved; (v) the criteria for determining whether the threshold for maximum site capacity has been met or exceeded and the process for communicating additional resources needed in order to participate in a new protocol and/or process for communicating that a site does not have the capacity to add an additional protocol; (vi) the process for assessing and evaluating potential PS sites; please do not identify any PS sites in the application; and (vii) close-out procedures for poorly performing CTU elements (i.e., CRSs, Laboratories, Pharmacies, etc.).

Sub-section E. Community

Describe (i) plans for community engagement consistent with GPP, including organizational charts; (ii) the role of CAB(s) and how the CAB(s) will support all CRS(s) and their populations(s); (iii) existing relationships between the CRS and community(ies) in which the research will be conducted, include information on nature and length of relationship as well as any outreach conducted to date; (iv) dedicated staff from the CRS, if any, that will support community activities and a description of their roles and responsibilities; (v) CAB composition including process for elections, jurisdiction, representation, function, work products, resource requirements and frequency of meetings; (vi) the plans for training CAB members including mentoring and continuing education; and (vii) communication with the CTU Administrative Office and the CRS; and (viii) the process for determining the level of financial support that will be provided by the CTU for CAB activities and how that level of support will be communicated to the CAB in a transparent manner and reassessed throughout the project period.

Sub-section F. Pharmacy

Describe (i) the overall CTU pharmacy structure and how this structure will support the pharmacy activities conducted at the CTU and each individual CRS, specify which (if any) activities are centralized, a diagram showing the relationships of each pharmacy is recommended; (ii) provide a staffing plan including a detailed description of lines of authority for pharmacy activities including required staff certifications. The staffing plan should reflect how the Pharmacist of Record will be integrated into CTU organization and management; (iii) plans for a staffing structure with roles and responsibilities of essential pharmacy personnel including a short summary of expertise and certification, and (iv) the plan(s) for CTU staff oversight of pharmacy operations and communications.

Describe pharmacy performance and experience with the U.S. FDA and other applicable regulatory agency (i.e., European Medicines Agency (EMA)) research over the previous 5 to 7 years and identify areas for improvement, if any. Describe the approach for optimizing efficiencies to support proposed clinical trials networks by resource sharing, centralizing activities, implementing cost containment measures, or other innovative approaches. List any applicable pharmacy certifications and/or accreditations. Describe previous experience of each pharmacy with regulatory agency inspections, if applicable.

Sub-section G. Laboratory

Describe (i) the CTU laboratory structure and how this structure will facilitate the research conducted at the CTU, specify which (if any) activities are centralized, a diagram showing the relationships of each laboratory is recommended; (ii) Provide a staffing plan including a detailed description of lines of authority for laboratory activities including required staff certifications. The staffing plan should reflect how the laboratory will be integrated into the CTU organization and management; (iii) the plan(s) for CTU staff oversight of laboratory operations and communications; (iv) and the plan for interactions with the clinical trials network Laboratory Center (LC).

Describe (i) the approach for specimen management including receipt, processing, storage, testing, reporting results, tracking, and shipping; (ii) identify which CRS(s) the laboratory facilities will support; and (iii) the approach for optimizing efficiencies to support proposed clinical trials networks by resource sharing, centralizing activities, implementing cost containment measures, or other innovative approaches.

Provide dates of current laboratory certifications/accreditations for each proposed CRS (i.e., College of American Pathologists (CAP), Clinical Laboratory Improvement Amendments (CLIA), National Accreditation Board for Testing and Calibration Laboratories (NABL), Swiss Accreditation Service (SAS), etc.)

Performance and Experience. Describe past laboratory performance and experience over the previous 5 to 7 years with U.S. FDA regulated research as well as non-U.S. regulated research (i.e., EMA) and identify areas for improvement, if any. Describe the approach for optimizing efficiencies to support proposed networks by resource sharing, centralizing activities, implementing cost containment measures, or other innovative approaches. Describe previous experience of each laboratory with regulatory agency inspections, if applicable.

Sub-section H. Data Management

Describe (i) the overall data management structure including a detailed description of lines of authority, and specify which (if any) activities are centralized; (ii) staffing plans with roles and responsibilities of essential data management personnel including assurance of data quality; (iii) the plan for effective interactions between the SDMC and local data management facility; (iv) data entry procedures from capture of source data to electronic case report form (eCRF); (v) the current information technology (IT) infrastructure and a plan for ensuring confidentiality, data integrity and security including processes to monitor and restrict access, and data back-up systems; and (vi) how access will be provided for NIAID monitoring contractors to Electronic Health Records (EHR), if applicable.

Sub-Section I. Regulatory Assurance

Describe regulatory requirements for protocol approval and implementation. Include details of (i) national, central, or local IRB and other regulatory requirements; (ii) average timeline for protocol approval based on past experience; (iii) challenges and other unique requirements that may have impacted protocol approval and implementation; and (iv) strategies to overcome regulatory challenges to facilitate protocol approval and implementation.

Describe the plan for ensuring compliance with FDA/ICH GCP, NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements as well as national and local regulatory authorities. Describe how each CRS will ensure that CRSs stay current with local and national regulations and changes.

Describe the process for ensuring regulatory agency inspection readiness. Describe experience over the previous 5-7 years with regulatory agency inspections and outcomes.

Sub-Section J. Training and Mentoring

Describe (i) how training needs will be assessed for all elements of the CTU; (ii) how training content will be developed/decided; (iii) how training needs will be reviewed, evaluated, and modified; (iv) how training will be delivered; (v) plans for mentoring new staff and providing continuing education for existing staff; (vi) training process and assessment of ability for staff to perform their roles within the CTU/CRS; and (vii) the process of documenting staff training.

Describe CTU and CRS plans to mentor/train early-stage investigators, investigators of both genders and underrepresented racial and ethnic backgrounds, investigators representing populations disproportionately affected by HIV/AIDS and investigators from resource-limited settings.

Sub-section K. Quality Management

Describe (i) the overall quality management plan and structure for all parts of the CTU including a detailed description of lines of authority; specify which (if any) activities are centralized; (ii) the duties and responsibilities of essential quality management personnel; and (iii) a plan to perform ongoing day-to-day quality checks as well as retrospective, objective, systematic, and periodic reviews of trial-related activities to ensure compliance with protocols, FDA/ICH, GCP, and NIAID requirements. Include the process, metrics, frequency of evaluation and documentation of findings, corrective and preventative action (CAPA) processes and continuous quality improvement activities that support data completeness and data integrity, and how modifications to quality management will be determined and implemented.

Pharmacy Quality Management: Describe (i) the requirements and processes for developing and implementing pharmacy Standard Operating Procedures (SOPs); the approach for managing pharmacy activities including study product receipt, storage, preparation, labeling, dispensing, final disposition, record keeping and accountability, participant counseling activities, if applicable; (ii) how these processes support applicable laws and regulations and (iii) a comprehensive pharmacy quality management program including a detailed plan containing quality control (QC) and quality assurance (QA) activities, processes, and procedures.

Laboratory Quality Management. Describe (i) the requirements and processes for developing and implementing laboratory SOPs; (ii) how these processes support applicable laws and regulations; and (iii) challenges and solutions for getting materials (e.g., test kits) into the country and specimens out of the country (if applicable); and (iii) the approach for ensuring GCLP compliance of the laboratories and all associated clinics where laboratory testing, including all point-of care testing, is performed.

Sub-section L. Clinical Research Site(s) (CRS)

Label each individual CRS (up to 8) with the site name and current NIAID CRMS site ID, if applicable, using the following outline as guidance:

Organization Structure: Describe (i) the CRS structure including a detailed description of lines of authority; a diagram showing the roles and lines of authority within each CRS is recommended, reflecting support commensurate with the size and scope of the CRS; and; (ii) plans for a staffing structure with roles and responsibilities of the CRS Leader and other CRS personnel. Please expand on the CRS Leader’s scientific contributions, leadership experience, and clinical research management and oversight of IND level multi-site clinical trials in the previous 5 to 7 years.

Proposed Research Priority Areas: (i) Identify the proposed NIH HIV/AIDS Clinical Trials Network(s) for each CRS and justify the proposed network affiliation; (ii) identify and expand on potential trial participants (e.g., demographics, incidence and prevalence of HIV/AIDS) based on demonstrated experience working with these populations and describe overall recruitment and retention plans per CRS; and (iii) describe existing and proposed community engagement plans.

Administration: Describe (i) how activities will be coordinated across multiple clinical trials networks, if applicable; (ii) innovative approaches for optimizing efficiencies to support proposed clinical trials network(s); and (iii) the approach for ensuring that protocol activities are conducted in accordance with FDA/ICH GCP, NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements as well as national and local regulatory authorities.

Performance and Experience: Describe (i) past performance and experience as a CRS or equivalent over the previous 5 to 7 years, including, but not limited to, types of studies conducted, enrollment and retention, data quality metrics, and timeliness of protocol implementation and execution; (ii) strengths in conducting complex clinical trials; (iii) challenges experienced in conducting complex clinical trials. Include details of any sponsor, self-imposed, or other actions taken to prevent or address performance, regulatory compliance, or other significant issues affecting participant safety or operations, as well as activities undertaken to overcome those challenges; (iv) Describe previous experience of each CRS with regulatory agency inspections, if applicable.

Letters of Support:

Provide letters of support necessary to demonstrate the commitment of collaborators. Do not submit letters of network support.

Progress Report Publication List:

Provide the requested information in the application instructions with the most recent publications and patents first.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

Other Requested Information

For Renewal applications with ongoing clinical studies, applicants must include a list of all ongoing clinical studies and/or the unique ClinicalTrials.gov identifiers. All information must be combined in one single attachment using the file name "ongoing Clinical Studies". If appropriate, please indicate for each study the NIAID Division of AIDS (DAIDS)-defined study status (https://rsc.niaid.nih.gov/networks-protocol-teams/developing-protocols).

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Although applicants must be prepared for clinical trials, definite plans for such involvement will not be possible at time of application. A Study Record MUST not be completed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

Both Renewal and New Applications must add and complete the Delayed Onset Study record and must check box "Anticipated Clinical Trial?".

Study Title-- use: "Multiple Delayed-Onset Studies"

Justification Attachment: Indicate each clinical study protocol developed during the project period will be subject to approval through a procedure that involves an initial concept submission and subsequent review by the HIV/AIDS clinical trials network. If the concept receives approval, the next stage will be development of the protocol, which also must undergo review and approval prior to implementation through the HIV/AIDS clinical trials network.

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

• Awards issued under this FOA will be incrementally funded awards for project periods of up to 7 years. Multi-year funded grants will not be awarded.
• Grants awarded under this FOA will be excluded from automatic carryover all carryover requests must be approved.
• Grants awarded under this FOA will not be provided the authority to automatically extend the final budget period one time for up to 12 months beyond the original expiration date shown in the Notice of Award all extensions, including the first extension, will require approval.
• Progress and financial reporting will be required and reviewed annually.
• All funds must be expended within the approved project period.

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process.

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

For this particular announcement, note the following:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will address if applications appropriately address the overall structure and function of the CTU as well as the demonstrated experience and capacity to implement, manage, recruit and retain the key populations into the clinical trials network protocols. Attention to the FDA/ICH GCP, NIH/NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements as well as national and local regulatory authorities is a priority.

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

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

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

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this FOA:

How well is the CTU positioned to contribute to the proposed network research priority areas? How effectively does the CTU structure demonstrate a cohesive, synergistic, and integrated unit, and is the integration evident within each of the elements and across the entire CTU?

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

With regard to the proposed leadership, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this FOA:

Does/Do the PD(s)/PI(s) and other key personnel plan to devote sufficient effort to perform his/her role commensurate with the size and scope of the CTU?

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this FOA:

Does the application provide innovative plans to share resources and contain costs?

Does the applicant propose innovative approaches to reach, recruit and retain a diverse and representative population to support the proposed HIV/AIDS clinical trials network priority areas?

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this FOA:

Is there an appropriate and clear organizational structure for the CTU commensurate with the size and scope of proposed CTU?

Are there adequate lines of authority and strong feasible governance plans for the CTU? Is there an appropriate staffing structure that capitalizes on the experience and expertise of the CTU PD(s)/PI(s) and key personnel?

Is the financial management plan adequate with respect to the size and scope of the CTU? Are appropriate fiscal management plans and processes proposed to establish sub-contract agreements, to allocate resources/protocol funds in a transparent manner?

Are the plans for communications within the CTU adequate?

Does the CTU have a robust plan for evaluation including assessment and monitoring of capacity, and strategies for improving performance across all elements of the CTU?

Are there appropriate plans to engage and receive input from the community?

Are there robust procedures from capture of source data to electronic case report forms?

Are training and mentoring plans appropriate?

Are plans for operation and management of the Pharmacy appropriate?

Do the CTU Quality Management Plan(s) and approaches promote regulatory compliance of clinical trials?

Are the CRSs well positioned to contribute to the proposed research priority areas based on demonstrated experience conducting complex clinical trials in relevant participant populations?

Are the CRS recruitment and retention plans appropriate to recruit research participants required for the proposed clinical research?

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international CRS(s) is/are proposed, does the application adequately address the complexity of executing the clinical trials?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this FOA:

Have the facilities been shown to be sufficient to support the proposed research priority areas to be addressed by the CTU?

Has the CTU demonstrated the ability and capability to administer and conduct multi-site clinical trials of HIV/AIDS and associated diseases?

Is there demonstrated, sufficient capacity to provide effective administrative, financial and managerial support for a highly complex clinical trials network including subcontracting, and information technology access and resources?

How well does the CTU demonstrate ability to effectively work within their regulatory environment, including maintaining compliance and keeping current with new regulations?

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

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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

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

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

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

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

Not Applicable

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

Not Applicable

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

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

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

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

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

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

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council . The following will be considered in making funding decisions:

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

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

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

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

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

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

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

For all Clinical Trial FOAs, use the Clinical Trial text insert.

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

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

PD(s)/PI(s) will have primary responsibility for the overall activities and performance of the CTU, including, but not limited to:

• Implementation of the clinical research protocols for the CTU-affiliated HIV/AIDS Clinical Trials Network(s).
• Developing and implementing strategies at each CRS (and PS site(s), if applicable) for the recruitment, screening, enrollment, retention and long-term follow-up of study participants appropriate to the conduct of the proposed research.
• Maintaining close communication and coordination with the LOC, LC, and SDMC for the network(s) with which the CTU/CRS is affiliated.
• Ensure performance monitoring and evaluation of CTU elements.
• Knowledge, acceptance and compliance by all CTU elements with the policies, procedures and bylaws of the NIAID clinical trials network(s), including: network policies and procedures for the collection, recording, storage and reporting of clinical trial data, sharing of research data and research resources, the research priorities of the NIAID and the affiliated networks; and performance standards established by the NIAID and the affiliated clinical trials networks.
• Ensuring that the CTU has investigators and appropriately trained and qualified staff with demonstrated expertise in conducting HIV/AIDS multi-center clinical trials.
• Ensuring implementation of clearly-defined organizational and communication plans and standard operating procedures to ensure close supervision and oversight of the day-to-day activities of the CTU, CRS (and PS site(s), if applicable).
• The receipt and appropriate administration of core funding to establish and maintain a minimal level of clinical research activities.
• The receipt and appropriate administration of protocol funding provided by either NIAID or the clinical trials network(s) to implement network-specific clinical protocols.
• Obtaining approval from NIAID to begin clinical research at the CRS. All CRS(s) are also required to complete DAIDS Protocol Registration for all clinical protocols in accordance with current NIAID policy and procedures prior to study initiation.
• Ensuring compliance with all Federal regulations for human subjects, investigational agents and devices, FDA/ICH GCP, NIAID Research Rules and Policies, DAIDS Clinical Research Policies, clinical trials network(s) requirements as well as national and local regulatory authorities for human subjects, investigational agents and devices.
• Ensuring compliance with the NIAID and clinical trials network(s) laboratory standards including participation in Quality Assurance (QA) programs and maintaining appropriate certification.
• Ensuring that the CTU develops, implements, and oversees a comprehensive Clinical Quality Management Plan for all elements of the CTU.
• Ensuring cooperation with the NIAID Clinical Site Monitoring/Auditing representatives, other NIAID authorized groups, or regulatory agencies.
• Implementing a plan to achieve community partnership in CTU activities.
• Implementing a plan for communicating study results to study staff, participants and the community as soon as possible after protocol unblinding or after receipt of the results summary from the LOC.
• Compliance with all adverse event reporting requirements designated by the NIAID and affiliated HIV/AIDS Clinical Trials Network, including, but not limited to the established policies and procedures delineated in the "Expedited Adverse Experience Reporting Policy .
• Ensuring that the CTU provides information requested by NIAID or affiliated HIV/AIDS Clinical Trials Network in a timely manner.
• Ensuring compliance with the policies and procedures set forth by the HIV/AIDS Clinical Trials network(s) and the NIAID regarding presentation and publication of major findings in the scientific literature. 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 HHS, PHS, and NIH policies.

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

NIAID Program Staff. NIAID staff assistance will be provided by an NIAID Program Officer along with other NIH staff. These staff will be identified at the time of award and their roles and responsibilities will be addressed in the Notice of Award. These NIAID staff members will have substantial scientific/programmatic involvement during the conduct of this activity through provision of technical assistance, advice and coordination above and beyond the normal program stewardship role for grants. The role of the NIH staff, as described throughout these terms and conditions of award, is to assist and facilitate the activities necessary to execute the research agenda, not to direct the specific research.

• Assure that network research efforts are consistent with that of the NIAID agenda for clinical research and complement those of other NIH and NIAID programs.
• Facilitate coordination among the NIAID- and other NIH-supported clinical trials networks, and research groups, and other U.S. Government agencies promoting collaborations and facilitating information exchange.
• Communicate the NIAID scientific priorities.
• Track protocol development, implementation, and study conduct.
• Attend and interact at meetings, trainings, and conference calls.
• Serve as resources for scientific and policy information.
• Organize meetings to facilitate exchange of information, including network meetings.
• Coordinate network community engagement outreach activities with other NIH-supported engagement outreach activities.
• Oversee contract resources that facilitate the provision of investigational agents or to meet needs identified by the NIAID Strategic Working Group (SWG) or other advisory bodies.
• Participate in the presentation of research results, including publications.
• Retain the option to recommend reduction of support from any cooperative agreement that substantially fails to achieve its goals or fails to comply with the Terms and Conditions of the award.
• Under urgent public health situations, the NIAID may re-direct funds or provide additional funds to individual awards to support research of direct relevance to the emergency.

NIAID will serve as a liaison between pharmaceutical companies, the FDA, and clinical trials network(s) investigator(s) and/or partners. In accordance with NIH policy, NIAID will ensure that all clinical trials performed through the CTU are conducted in accordance with FDA/ICH, GCP and applicable Federal regulations.

Clinical Site Oversight. The NIAID will review and approve all CRS(s) (and PS site(s), if appropriate) prior to initiation of any NIAID-sponsored clinical research. NIH staff may conduct site visits to the CTU or elements for the purposes of assessing site readiness, or to evaluate ongoing operations, clinical research processes and recordkeeping, or to investigate significant findings on monitoring or other Network LOC/LC/SDMC reports. The NIAID staff or designee will also review site visit reports and reserves the right to independently monitor the CRS(s) in accordance with FDA/ICH GCP guidelines. In collaboration with the clinical trials networks, NIAID reserves the right to temporarily suspend a trial at a CRS based on pervasive, significant noncompliance.

Site and Laboratory Monitoring. NIAID oversees an external clinical site monitoring contract that evaluates FDA/ICH, GCP, regulatory compliance, protocol implementation, internal quality assurance, and test article accountability at the clinical research sites for clinical trials conducted under IND/IDE. When NIAID is not the regulatory sponsor, clinical monitoring support is provided based on a case-by-case determination.

Pharmaceutical Support. For studies in which the NIAID is the IND or IDE sponsor, NIAID staff and/or contractors will provide consultation with CTU staff on study product-related issues including manufacturing, preparation, administration and availability of active dosage forms and placebo. NIAID staff and/or contractors may also interact with pharmaceutical company collaborators to facilitate adequate and timely supply of study product and oversee the distribution of study product to the clinical research sites. When NIAID is not the regulatory sponsor, pharmaceutical support is provided based on a case-by-case determination.

Training. NIAID will provide a variety of training activities to appropriate network personnel to help the network ensure that consistent standards for protection of human subjects, conduct of clinical trials, and documentation are achieved. This training may be developed in conjunction with clinical trials network(s) and be provided directly by the NIAID staff or through contractors. Training areas will include, but not be limited to, regulatory requirements, GCP, adverse event reporting, quality management, human subject protections, and NIAID policies and procedures. Some training or retraining may require mandatory attendance.

Safety Reports. For studies in which NIAID is the IND or IDE sponsor, NIAID will assume responsibility for the reporting of safety information in accordance with FDA requirements and preferences. In order to provide for consistent reporting of serious adverse experiences across clinical trials groups, NIAID shall provide current policies and procedures that govern the reporting of adverse events in NIAID-sponsored trials. The NIAID staff and/or contractors will provide training in the specific procedures and requirements for adverse event reporting for clinical trials conducted under this award.

Protocol approval. NIAID will review and provide approval for all protocols prior to implementation.

Safety Monitoring. NIAID participates in the development of appropriate safety monitoring plans for all planned clinical trials and must approve the plan for all trials involving investigational drugs, devices, or biologics and other clinical research perceived to involve more than a minimal risk. The frequency and intensity of safety monitoring will be based on individual study characteristics and past experience with study products and may require review by an Independent Safety Monitor, Independent Monitoring Committee (IMC), Safety Monitoring Committee (SMC) or Data and Safety Monitoring Board (DSMB). NIAID Medical Officers will be part of network-organized protocol safety review teams to monitor the safety and efficacy of the intervention(s) for ongoing studies and will be provided with appropriate reports. Approval of the final monitoring plan, including the composition of the review committee, by NIAID is required prior to study initiation. NIAID independently supports DSMBs that oversee Phase IIb/III and other select clinical trials at the discretion of NIAID.

Protocol Termination. The NIAID reserves the right to terminate or curtail a clinical study or temporarily suspend or terminate the participation of a CRS or PS site for any of the following reasons:

• risk to subject safety;
• failure to comply with Good Clinical Practice, federal regulations, or Terms of Award;
• risks that cannot be adequately quantified;
• ethical concerns raised by the local community or local medical care/health care authorities;
• failure to remedy deficiencies identified by site monitoring teams; and
• failure to meet NIAID and clinical trials network performance standards

Data Access. The awardees retain the rights to the data, consistent with current DHHS, PHS, NIH and NIAID policies; however, NIH will have access to all data generated (raw and analyzed) and may periodically review it. This includes a review of data as recorded on the case report forms or in the central database, and external checking against the original source documentation as required by federal regulation and NIAID as the IND sponsor. NIAID may request from the CTU specific data analysis needed for programmatic activities or for issues related to NIAID plans with other partners. The NIH may provide public access to selected data sets generated with the use of public funds within a reasonable time after the primary analysis and publication. 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. NIAID will develop a memorandum of agreement with the owners/providers of applications/systems that share data/information with the CRMS.

Areas of Joint Responsibility:

• Protocol Development. The LOC will assemble and manage protocol teams, that could include CTU/CRS staff. NIAID staff and support contractors, as required, will participate in these teams.
• Oversight of Clinical Trials. On an ongoing basis, the CTU, CRS and NIAID staff will jointly evaluate the progress of clinical trials, including enrollment milestones, site and laboratory quality, and data quality. NIAID and NIAID contractors may audit sites, SDMC, and laboratories to assess FDA/ICH, GCP and data quality and integrity.
• Community Engagement. Representatives of CRS Community Advisory Boards (CABs) will participate with NIAID staff and network representatives to:
• Review and assess the community engagement program and activities, to include identifying strengths and weaknesses and recommending improvements
• Performance Assessment. NIAID, in conjunction with the affiliated HIV/AIDS Clinical Trials Network, will assess the performance of the CTU in an ongoing manner. The affiliated HIV/AIDS Clinical Trials Network will develop an evaluation plan with defined goals and measurable objectives linked to specific performance metrics as appropriate to the network clinical research area(s) and include remedial actions for sites failing to meet acceptable standards. Each CTU is expected to adhere to the performance standards of the networks with which they propose affiliation. CTU elements that fail to meet performance standards may be subject to withdrawal of funding.
• External Advisors. NIAID may seek evaluation, advice and recommendation concerning ongoing and planned research activities of the CTU and affiliated HIV/AIDS Clinical Trials Network(s) from external advisors. Advisors will not include key personnel or collaborators of the key personnel of any of the awardees.

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 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 awardees. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16

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

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

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

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

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

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

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

Bola Adedeji, R.Ph., M.S.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3055
Email: [email protected]

Robert Unfer, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5035
Email: [email protected]

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: [email protected]

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

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