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 for a HIV Prevention Clinical Trials Network Leadership and Operations Center (LOC). The LOC will be responsible for the overall administrative and scientific leadership for the HIV Prevention Clinical Trials Network.

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’s overall HIV prevention research goal is to deliver products and strategies that reduce HIV incidence at a population level. In order to accomplish that goal the research must focus on advancing a range of products and strategies to meet the needs of populations vulnerable to HIV infection.

New antiretroviral (ARV)-based prevention methods including HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) products and delivery methods are needed to be able to meet the overarching NIH prevention goals. Those products will preferably achieve prevention of HIV acquisition from all potential routes of exposure (i.e., systemic protection) and minimize the need for consistent medication adherence that represents a challenge for daily, oral PrEP effectiveness. However, products that do not achieve complete systemic protection but do address an agreed upon compelling specific public health need can be considered on a case-by-case basis if the scientific data support moving them forward to clinical testing.

Multipurpose prevention technologies (MPTs) may be an important strategy to prevent HIV, especially in adolescents and young women. The ability to offer effective contraception in combination with an HIV prevention product may increase the product desirability and uptake by meeting both critical needs simultaneously. MPTs might also include prevention of other STIs. The choice of which STI to target should be based upon prevalence in the target population and potential public health impact.

NIH also recognizes the importance of integrated biomedical and socio-behavioral prevention strategies in the efforts to reduce HIV incidence at the population level. Targeting effective prevention packages to key populations requires knowledge of local and regional epidemiology, social and sexual network dynamics, and related behavioral and social components, as well as understanding of service delivery and financing. This research requires a multidisciplinary team approach and will be best accomplished by working in partnership with implementing agencies and organizations.

The specific scientific priorities of NIH that will be addressed by the LOC’s proposed scientific research agenda are as follows (not in priority order):

Novel ARV-based HIV Prevention Methods and Delivery Systems

Focus on delivery methods that help to address the challenges of adherence including and not limited to long-acting agents and sustained release systems is encouraged. The delivery method should achieve systemic protection from infection or protection from all routes of sexual exposure for the target key population. However, products that do not achieve complete systemic protection but do address an agreed upon compelling specific public health need can be considered on a case-by-case basis if the scientific data support moving them forward to clinical testing.

Key populations to be considered are young cisgender women in Southern Africa, men who have sex with men (MSM), transgender people, persons with injection and non-injection substance use and substance use disorders, sex workers, groups demonstrating age, racial/ethnic, or gender-based disparities, adolescents and pregnant women. The following types of evaluations of these products are considered responsive to this FOA:

• Early stage acceptability/desirability research to optimize and select candidate products and delivery systems
• Pharmacokinetic/pharmacodynamic assessments
• Safety evaluation to include maternal and pregnancy outcomes
• Efficacy testing
• Bridging studies for additional populations

As part of any ARV-based prevention product development there is a critical need to determine end-user preferred characteristics using appropriate methodologies to increase prevention product uptake recognizing that there is a significant gap between intention/acceptance and uptake. Prevention product desirability is the goal and the proposed research should include expertise and use of methodologies from the disciplines of behavioral and social science as well as human-centered design by using ethnographic and other such techniques, as appropriate.

Multipurpose Prevention Technologies (MPTs)

MPTs are defined as the coformulation and/or simultaneous delivery of a licensed pregnancy and/or STI prevention strategy with a HIV prevention method.

Included are the following types of clinical product development activities for MPTs:

• Early stage acceptability/desirability research to optimize and select candidate products and delivery systems
• Pharmacokinetics/pharmacodynamic assessments
• Safety
• Efficacy

As with ARV-based prevention product development, there is also a need with MPTs to determine end-user preferred characteristics using appropriate methodologies as described above.

The HIV prevention component of MPTs must impart or confer systemic protection against HIV acquisition. However, products that do not achieve complete systemic protection but do address an agreed upon compelling specific public health need can be considered on a case-by-case basis if the scientific data support moving them forward to clinical testing.

Development of MPTs will also require substantial engagement of regulatory agencies in order to chart a Product Development Plan that will be acceptable from a regulatory requirement perspective.

Integrated Biomedical and Socio-Behavioral Prevention Strategies

In partnership with other NIH Institutes and Centers (ICs), US governmental agencies, and non-governmental foundations and organizations, NIAID seeks to pioneer and improve the effective delivery of proven prevention tools through strategies that integrate and optimize their implementation. Examples of potential populations of high importance for integrated prevention strategies include:

• Young, cisgender women in Southern Africa
• Men who have sex with men (MSM)
• Transgender people
• Persons with injection and non-injection substance use and substance use disorders
• Sex workers
• Groups demonstrating age, racial/ethnic, or gender-based disparities in HIV prevention product use and outcomes
• Adolescents
• Pregnant women

Cross-network collaborative research area:

Research related to passive administration of antibodies will continue to be at the scientific interface of HIV vaccine- and non-vaccine prevention. Consequently, it is anticipated for this research area there will be continued productive collaboration and joint scientific leadership by NIH-supported networks devoted to clinical trials of HIV vaccines and non-vaccine prevention strategies. This includes passive immunization strategies to administer:

• single monoclonal antibodies
• combinations of multiple monoclonal antibodies of different specificities and binding sites or different protective mechanisms
• combinations of antibody molecules with antiretroviral drugs and other prevention modalities
• engineered molecules derived from or related to antibodies that have novel binding specificities, altered half-life or host interaction profiles, or altered mechanisms of protection
• vectors encoding one or more antibody or antibody-related molecules capable of sustained in vivo antibody expression
• polyclonal antibody mixtures derived directly from humans or from biotechnological engineering
• When addressing clinical research questions in specific populations, the two leading networks will be expected also to collaborate with additional population-specific research networks as needed to ensure access to the required scientific and clinical expertise.

The HIV Prevention Clinical Trials Network may have the opportunity to contribute to the research agenda for support of the development of strategies, interventions, and products against other infectious diseases (not listed above) and to implement clinical trials in support of this agenda. 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), a Laboratory Center (LC), a Statistical 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 on clinical trials, clinical research studies that aren't NIH-defined clinical trials are also in scope when undertaken 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 systems 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:

• Safety Oversight Committees: NIAID oversees the safety of all participants in clinical trials funded by NIAID. Generally, NIAID Division of AIDS (DAIDS) will provide NIAID-convened Data and Safety Monitoring Boards (DSMBs) to monitor 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 study products, and clinical site monitoring. In addition, there are resources for clinical laboratory quality assurance and proficiency testing. A detailed description of these NIAID contract resources can be found at this website.

The LOC will be responsible for overall administrative and scientific leadership for the network, as well as oversight and evaluation of all network activities, including developing and refining the research agenda, prioritizing research concepts, efficiently managing the development of clinical protocols, overseeing compliance with regulatory standards, implementing and completing clinical trials and ensuring timely publication and communication of results. The LOC is also responsible for the following:

• Governance: Integral to the success of the network is establishing clear governance structures, including effective communication and decision-making plans, lines of authority, plans for coordinating and collaborating effectively with external collaborators and NIAID and IC partners, and resource distribution policies.
• Research Agenda: The LOC, in collaboration with the LC and SDMC, articulates the network’s scientific agenda, establishes a framework for the initial studies, and plans for future studies. A research agenda is the broad strategic plan to address the stated research priority areas. The LOC is expected to actively engage researchers and communities within and outside of the network in establishing and refining the research agenda. The LOC will also work closely with NIH Program Staff to ensure that the research remains aligned with NIAID and partner IC’s research priorities.
• Innovation: The LOC is encouraged to explore innovative approaches, including public-private partnerships that will have a broad impact on the overall field of HIV clinical research.
• Clinical Operations: The LOC provides operational support, management, and oversight for the network’s clinical studies and trials. This requires close coordination with the LC, SDMC, network-affiliated CTUs and CRSs, and NIH staff and clinical research support programs. The LOC clinical operations provide leadership on protocol development and implementation and are responsible for clinical site selection, qualification, and management. Once protocols are underway, the LOC is responsible for tracking progress and coordinating efforts to efficiently complete trials and disseminate results.
• Network Management: The LOC will develop policies, by-laws, standard operating procedures (SOPs), budgets, and communication plans for the network. It will work synergistically with NIAID and the CTUs and CRSs to facilitate protocol implementation and progress through study completion. The LOC is expected to employ strong project management practices for management, oversight, communication and coordination of long-term and day-to-day activities associated with network clinical studies, including: development of protocol-specific project plans that establish realistic milestones, timelines and resource needs; ongoing tracking, evaluation, adjustments and reporting; and implementation of contingency plans.
• Quality Management: The LOC is expected to ensure the overall Clinical Quality Management (CQM) of all activities through Quality Assurance and Quality Control processes and procedures. The purpose of CQM is to ensure protocol regulatory compliance, ensure protection of participants and data integrity, and compliance with all applicable regulatory requirements. The LOC will also be responsible for enabling sponsor/client audits and inspection by regulatory authorities.
• Training and Mentoring: The LOC is expected to provide the necessary and appropriate training for staff, and will be responsible for ensuring that training needs are met across the network, including but not limited to, protocol training for participating sites and other key stakeholders. The LOC will also promote mentorship and involvement of early-stage investigators.
• Clinical Research Sites (CRSs): Due to the diverse nature of network studies and required patient populations, a major activity of the LOC is establishing efficient processes for identifying, qualifying, and approving clinical research sites to address specific clinical trials network needs.
• Network Meetings. The network will hold an annual meeting in the Washington, DC metropolitan area to share recent findings and facilitate collaborations. All key personnel and NIH program staff are expected to attend and participate. External Advisors may also attend the program update portion of the meeting. These meetings will be held jointly or in coordination with other NIAID- or NIH-supported clinical trials network meetings when indicated. The meetings must be open to the public, although selected sessions may be indicated as invitees only upon approval of the NIAID Program Official. Invitee-only sessions must be open to all NIAID specified attendees, including contractors. Modifications to this minimum number of meetings or location will require a special waiver from the Director, NIAID Division of AIDS (DAIDS).

When additional clinical research sites are essential to meet individual protocol needs, the LOC is expected to evaluate all funded CTUs and CRSs. When appropriate, NIAID may approve additional protocol-specific clinical research sites on a case-by-case basis. It is expected that these protocol-specific sites will be affiliated with CTUs (either as a component of the grantee or a subcontract) or, in limited instances, subcontracted through the LOC.

External Interactions and Opportunities. The LOC 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. In addition, the LOC is expected to ensure maximal use of the specimens collected during the course of NIH-supported clinical studies by providing guidelines and processes for use during the conduct of the study and by coordinating access to the scientific research community after the study is completed.

The LOC will need to coordinate with NIAID groups including but not limited to: the NIAID Strategic Working Group (SWG), DAIDS Office of Clinical Site Oversight (OCSO), the DAIDS Clinical Laboratory Oversight Team (DCLOT), and the Office of HIV/AIDS Network Coordination (HANC).

Funding to carry out the network's research agenda falls into two categories:

Core Funds. NIAID will provide core funds directly to the LOC, LC, SDMC and network-affiliated CTUs on an annual basis. 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
• 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

Protocol Funds (PF). NIAID will provide PF to the LOC, LC and SDMC on an annual basis. In addition, NIAID anticipates providing PF directly to network-affiliated CTUs on an annual basis. PF provides support to conduct 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 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 (protocol-specific)
• Good and Services Tax (GST) where required
• 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
• 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. For protocol-specific CRSs, NIAID anticipates providing PF salary support to the network LOC, which will in turn provide it to protocol-specific CRSs only if they are not affiliated with a CTU. CTUs/CRSs will receive non-salary PF support through the associated network LOC.

Distribution of Protocol Funds to Network-Affiliated LCs and SDMCs

PF will be distributed to the LCs and SDMCs directly from NIAID prior to enrollment of study participants following the process described above.

PF may also be provided to the LOC for its use and distribution to the LC and SDMC to provide additional support for protocol-related expenses for activities that are not directly related to participant accrual.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

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

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:

Dharmendar Rathore, Ph.D.
Telephone: 240-669-5058
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 Proposed Leadership and Operations Center (LOC) one required - 12 pages

Sub-section B. Scientific Leadership: Structure and Governance one required - 12 pages

Sub-section C. Clinical Research Agenda one required - 30 pages

Sub-section D. Training and Mentoring one required - 12 pages

Sub-section E. Evaluation and Improvement one required - 6 pages

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

Sub-section G. Clinical Operations one required - 30 pages

Sub-section H. Collaboration with the Statistical and Data Management Center (SDMC) one required - 6 pages

Sub-section I. Collaboration with the Laboratory Center (LC) one required - 6 pages

Sub-section J. Collaboration with the Clinical Trials Units (CTUs) and Clinical Research Sites (CRSs) one required - 6 pages

Sub-section K. Communication, Collaboration and Harmonization - one required - 12 pages

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:

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. Quality Management Plan

Provide a full LOC Quality Management Plan including quality control, quality assurance and quality improvement. If appropriate, provide an example protocol-specific Quality Plan for a protocol opened for enrollment since March 2018. (use filename: "Quality Management Plan").

Attachment 2. Sample Protocol Template

Provide a sample protocol template (use filename "Protocol Template").

Attachment 3. Procedures for Clinical Site Selection

Provide procedures for the selection of clinical sites (use filename "Clinical Site Selection").

Attachment 4. Procedures for Clinical Site Performance Evaluation

Provide procedures for clinical site performance evaluation, including how poor performance will be defined, and if appropriate, how it will be addressed (use filename "Clinical Site Performance").

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

In the biosketch describe the relevant experience of the PDs/PIs in leading and managing a complex clinical research program, including the roles and responsibilities served. Describe relevant expertise in protocol design, regulatory compliance, site selection, study implementation and coordination.

In the biosketch describe the experience of the project management staff, including roles and responsibilities served, and resource management expertise for clinical research programs of similar size and scope.

In the biosketch applicants should describe the extent of their expertise in working with commercial off-the-shelf (COTS) clinical trial management systems including Electronic Data Capture (EDC) systems.

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

The applicant should only request 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
• 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

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 as previously described.

If a single PD/PI is proposed, the PD/PI will be required to devote at least 6 person-months of effort to the project. If two or more PD(s)/PI(s) are named, each PD/PI must devote at least 3.6 person- months of effort to the project.

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: List and describe the scientific aims of the Leadership and Operations Center for the HIV Prevention Clinical Trials Network.

Research Strategy: The Research Strategy section must consist of subsections A-K as designated below.

Sub-section A. Overview of the Proposed Leadership and Operations Center (LOC)

Provide a high-level overview of the key clinical research questions in HIV prevention and explain how the LOC research agenda will address them. The Overview should articulate a coordinated research agenda, including the overall goals of the LOC and a discussion of priority setting, the proposed approaches, and an iterative reassessment of the plan. Explain how the LOC will be integrated with the SDMC, LC and CTUs/CRSs and leveraged to meet the goals of the overall network.

For renewal applications: Progress Reports should be included in sub-section A.

Sub-section B. Scientific Leadership: Structure and Governance

Describe the organization of the LOC and how the structure supports effective leadership of overall network activities. In this sub-section, applicants should:

• Describe the overall LOC structure including plans for a staffing structure with roles and responsibilities. Tables, diagrams, flow charts or organizational charts are strongly recommended. Provide an organizational chart(s) that identifies senior/key LOC personnel and briefly describe how structures in the LOC will interface with the network LC, SDMC and CTUs/CRSs;
• Describe the approach to governance of the LOC, including establishment of decision-making committees (including the EMC) and their composition, roles, responsibilities and decision-making authorities. Do not name or contact additional staff that are not already key personnel in the application.
• Discuss how the proposed governance structure capitalizes on the individual strengths of the key personnel to achieve the scientific goals of the network.
• Describe the approach to coordinating the functions of the LC and SDMC and plans for coordinating with the network-affiliated CTUs/CRSs.
• Describe the processes needed to establish priorities; to develop and review changing needs; to identify and coordinate changing network resources; and to develop plans for and implement discontinuation of unproductive or unneeded activities. Include within the discussion how these efforts will be coordinated with the LOC PD/PI, LOC committees, and clinical operations.
• Discuss the development of contingency plans and how efforts will be redirected in response to direction from the EMC.
• Discuss plans to exchange scientific and programmatic information with NIH and key stakeholders, to assess scientific progress, and to consider new research opportunities and potential avenues of collaboration.
• Describe the process for high-level scientific and administrative decisions for the network, including research prioritization, reassessment, and redirection, including specific information about key contributors.
• Describe processes for network-wide communications, including communications among and between the LOC, LC, SDMC and CTUs/CRSs, and specifically address how NIAID Program Staff will be incorporated into these communications. Do not name individual NIAID staff.
• Describe the structure and staffing plan for project management functions at the protocol level including plans for resources management, and processes for redirection of staff, funds and other resources.
• Describe established collaborations and provide proposed network collaboration plans, including plans for collaborating with other government-funded programs, non-government organizations, and pharmaceutical and medical device companies. Do not name or contact potential collaborators that are not already key personnel in the application or are not providing a letter of support.
• Describe plans for communicating and publishing research results from network studies.

Sub-section C. Clinical Research Agenda

Discuss knowledge gaps and future opportunities in the field of HIV prevention research and summarize the proposed scope of a HIV Prevention Clinical Research Agenda. Clearly describe strategic research plans for the agenda. Discussion should address flexibility in research direction to explore scientific opportunities and recent technologies as they arise. This sub-section is provided to describe goals and objectives within a single coherent research program of multiple priority areas.

• For each research priority area identified above in Section I, explain how each area fits within the applicant's overview of the HIV field and has potential to address or improve the challenges of HIV/AIDS, including in populations disproportionately impacted by HIV/AIDS. Provide milestones and timelines for completing key goals of the research agenda.
• Describe the general characteristics needed in each target population to address the research priority areas. Describe in general the scientific staff composition and types of unique expertise necessary to address the proposed approach as well as laboratory and site requirements. Indicate how these needs may evolve over the award period.
• Describe plans for community representation and indicate how these may evolve over the award period.
• Discuss how contributions by others were considered in developing the research agenda, how the research agenda will address key knowledge gaps and future opportunities in the field. Include descriptions of high-priority research areas.
• Describe how the proposed LOC structure will facilitate flexibility in responding to new HIV prevention-related scientific opportunities including processes to rapidly implement small proof of concept or phase I, single-site clinical trials when such trials of high priority are identified.
• Describe how research concepts are solicited, prioritized, and evaluated in relationship to the research agenda, including the process for the integration of novel ideas and expertise from outside the network.
• Describe the means for consideration and approval of 1) sub-studies not included in the original study proposal, and 2) access to specimens and data from existing protocols, from investigators both within and outside the network.
• Continuous refinement of the research agenda: describe the process and frequency for assessing the research plans and priorities, including plans to obtain external assessments of research. Discuss the processes for instituting major adjustments to the agenda in response to assessments. Describe how the decision-making committees will be evaluated and, if necessary, modified to best meet the needs of the network.
• Describe the process and frequency for assessing approved research concepts for scientific merit, feasibility, and priority throughout the life of the project.
• Provide plans for fostering relationships with representatives from other agencies, organizations and companies, as appropriate, to ensure access to products/tools to be studied and/or delivered.

Sub-section D. Training and Mentoring

Describe how the training needs of LOC scientific staff will be determined, provided and evaluated, and how necessary changes in training will be decided and implemented. Discuss how the LOC will coordinate across the network to ensure appropriate training needs are met.

Provide plans for clinical research mentoring opportunities and integration of early stage investigators, investigators of both genders and underrepresented racial and ethnic background, and investigators representative of populations and settings disproportionately affected by HIV/AIDS, including investigators from resource-limited settings.

Sub-section E. Evaluation and Improvement

Describe how the performance of the LOC will be evaluated and improved over the award period. Describe the process for re-evaluation of operational performance of the overall network in the conduct of network activities, including the financial management of network resources. Provide the criteria for reallocation, if necessary, of resources to ensure efficient resource management. Include a discussion of metrics that may be used to determine both productivity and quality of the results generated by the network over the duration of the award. Include information on how findings will impact adjustments to LOC and network activities and follow up evaluations. Describe processes for the resolution of performance problems for the network and proposed processes for the remediation/improvement of performance. Do not name or contact anticipated advisors; rather, list areas of expertise that will be sought, frequency of assessments, etc.

Describe the process, frequency and metrics of evaluation of data management at SDMC and site(s) and the quality of statistical support. Discuss the process for addressing outcomes, and resolution of performance findings.

Sub-section F. Quality Management

Describe the approach to quality management for LOC activities and LOC-coordinated management of efforts of the SDMC, LC and CTUs/CRSs needed for achieving and maintaining compliance with ICHE6, 21CFR Part 11, Good Documentation Practice (GDP), Good Manufacturing Practice (GMP), DAIDS Clinical Research Policies and Standard Operating Procedures (SOPs), and other standards.

Describe the coordination of the overall LOC Quality Plan with individual quality plans developed for each protocol. Address quality control procedures including real time systemic checks of protocol and regulatory adherence; quality assurance including regular auditing, and quality improvement based on evaluation and education.

Sub-section G: Clinical Operations

Structure and Management Plan

Describe the function of the LOC clinical operations (CO) in facilitating implementation of the clinical studies and clinical trials of the network's research agenda. Describe in detail how the CO will manage the day-to-day activities and how scientific and fiscal responsibilities will be coordinated across the network to achieve the scientific goals.

Describe the organizational structure for CO. Tables, diagrams, flow charts or organizational charts are strongly recommended. Provide a structure for and describe the financial management of network resources, including: lines of authority; decision making and management processes. Describe plans to ensure cost-effective use of CO resources and as applicable to solicit, evaluate, award, and manage subcontracts.

Protocol Development

Describe the proposed approach to developing clinical research concepts approved by the LOC into protocols and associated documents, ensuring adherence to NIAID DAIDS clinical research policies and SOPs, ICHE6, and 21CFR Part 11. Describe the decision-making process for each step in the protocol development process.

Provide the criteria upon which protocol investigators, protocol project managers, and protocol teams will be assembled to ensure strong scientific, clinical, and operational leadership. Describe means to access expertise in clinical site management, study product management, regulatory support (including support from non-U.S. regulatory agencies, where applicable), and industry liaisons, as appropriate. Discuss the roles and responsibilities of protocol development team members, representation from the LC and SDMC and CTUs/CRSs during protocol development and planning, and during the implementation and conduct of each protocol.

Discuss how project management plans linking resources to milestones will be developed, tracked, and monitored. Include a discussion of how realistic milestones and go/no-go criteria will be established, and how established plans, actual data, and future projections will be evaluated. Include a discussion of the development of contingency plans and the processes to adjust project plans.

Provide a general protocol development timeline starting with the approval for the clinical research concept and listing milestones up through final approval of the protocol by DAIDS and distribution to the sites. List the standard timeline for each milestone as well as for expedited protocol development. Include a discussion of the process for expedited development of high-priority concepts.

Describe how protocol budgets will be developed and how protocol funding will be linked to resource requirements. Describe the process for determination of salary and non-salary PF allocation to the CTUs/CRSs. Also describe the process for, and timing of, distribution of PF to the CTUs/CRSs and protocol-specific sites not affiliated with a CTU.

Describe the iterative Project Management Process with respect to study initiation, planning, execution and performance monitoring to ensure that individual studies stay on budget and that critical milestones are completed on a realistic schedule. Describe the process of identifying, allocating, and tracking of resources for individual protocols including: laboratory, data management, clinical sites, and the need for NIAID contract resources (clinical site monitoring, regulatory support, study product management, laboratory quality assurance/proficiency testing programs, etc.).

Discuss plans to ensure adherence to critical milestones and adjustments based on evaluation of projections against actual data. List the critical requirements that must be met to open the protocol to accrual.

Provide other relevant information on the Project Management Process including, for example:

• how study startup timeframe is determined,
• how deadlines for critical items such as Institutional Review Board (IRB) reviews and regulatory submissions are determined,
• how enrollment activities, timeframes, etc. are projected,
• how resource needs are determined and monitored,
• how effective lines of communication are developed and maintained across the study as resource needs change,
• how performance measures are assessed, and the information disseminated to identify areas of potential risks, and
• how risk mediation procedures for any action improvement are implemented.

Clinical Research Site Selection

Describe the approach for identifying and assessing clinical site capacity for protocols, for determining the need for additional clinical site capacity, and for addressing needs that arise during the project period of the award that cannot be met through the NIAID-funded clinical trials network sites. Describe the approach for adding clinical research sites that are not NIAID-funded clinical trials network sites, and how the LOC will ensure that these processes remain transparent to NIAID and the network-affiliated CTUs. Do not name specific CTUs/CRSs in the application.

Provide plans for communicating and coordinating with the CTUs/CRSs, affiliated laboratories, and NIAID clinical research support programs (e.g. monitoring, pharmacy, regulatory). Discuss how plans will translate to ensuring synergy among the clinical research sites and to ensuring a flexible structure capable of responding to new scientific opportunities.

Protocol Implementation

Describe the approach to implement and complete approved protocols, including: critical protocol implementation milestones/timelines; plans for modifying protocol implementation milestones/timelines including completing final study reports and publication.

Provide approaches for integration with NIAID contract resource programs.

Describe the process for fast tracking implementation of high-priority protocols.

Describe plans and procedures to identify and provide protocol-specific training. Include the source(s) of training; general format; plans for monitoring training needs; and how the need for retraining will be identified and implemented, if required.

Discuss the process for negotiating the following points prior to protocol implementation:

• ability to ship specimens for centralized short- and long-term storage, sample access, storage and disposition
• data access, storage and disposition
• scientific credit, publications
• regulatory support needed for international sites
• regulatory submissions

Discuss the approach to clinical research site performance evaluation, including how poor performance will be defined, and if appropriate, how it will be addressed.

Sub-section H. Collaboration with SDMC

Describe plans, processes and procedures for interacting and collaborating with the SDMC. Discuss how the LOC will facilitate the use of data systems by the SDMC that are compliant with 21 CFR and ICH guidelines. Describe coordination of activities with the SDMC staff including, but not limited to: protocol design, development, and implementation, data analysis, preparation of data summaries (within and across protocols), and publication of results. Describe the coordination process to ensure that protocol data management capabilities are coordinated with protocol development to ensure that implementation of trials occurs in a timely manner. Describe plans for coordination of responsibilities of the LOC and SDMC in study preparation at the data management and site level including protocol-specific training.

Describe the process for verifying that SDMC and clinical site capacity are available and sufficient to support implementation of protocols.

Describe plans for integrating and coordinating the LOC overall Quality Management Plan with the Quality Management Plan from the SDMC once awards for both FOAs are made.

Sub-section I. Collaboration with LC

Describe plans, processes and procedures for interacting and collaborating with the LC. Describe the collaboration with the LC in the evolution of the research agenda, and in development and implementation of protocols. Describe the process for projecting needs and costs for laboratory services including capacity to conduct routine and protocol-specific laboratory assays, conduct laboratory activation and training, and provide repository services.

Describe plans for LC involvement with local, regional and specialty laboratories.

Describe the process for tracking actual use of protocol-specific laboratory services compared to projected needs and adjusting capacity.

Describe plans for integrating and coordinating the LOC overall Quality Management Plan with the Quality Management Plan from the LC once awards for both FOAs are made.

Describe the process, frequency and metrics for evaluation of the LC. Describe the process for addressing evaluation outcomes and resolution of performance.

Sub-section J. Collaboration with CTUs and CRSs

Describe how the LOC will interact and collaborate with the CTUs and CRSs, including the following:

• conducting site feasibility assessments, including how site capacity, capabilities, and needs will be assessed
• soliciting, reviewing, and selecting CRSs to implement specific protocols based on objective data on the presence of the desired patient population and the ability to recruit, enroll, and retain research participants
• establishing timelines for CRS protocol activation including milestones, responsible persons, and how activation will be synchronized with protocol development and approval
• establishing procedures for development and delivery of protocol-specific training;
• providing support for CRS investigators in low and middle-income settings to engage and educate local Institutional Review Boards (IRB)/Ethics Committees (EC) and regulatory review committees to facilitate protocol review and approval
• providing safety oversight for study participants and compliance with all safety guidelines and regulations at all CRSs
• providing management of study products
• providing classification, labeling, documentation, shipping and tracking of clinical specimens
• verifying access to an affiliated laboratory capable of protocol-specified testing, as well as specimen processing, laboratory data management capabilities, shipment and storage of samples collected at the site
• identifying any country-specific regulations or laws that prevent or limit the shipment of study samples for testing or storage into and out of the country
• ensuring access to a secure pharmacy facility
• ensuring the ability to collect, process, analyze (if appropriate) and transmit data to the SDMC
• establishing plans and decision process for reducing research capacity including site closure if necessary
• describing plans to coordinate the LOC Quality Management Plan with individual quality programs in the CTUs and CRSs.

Sub-section K. Communication, Collaboration and Harmonization

Provide proposed LOC internal and external communication plans, including a description of functional roles and responsibilities.

Describe plans for community engagement, including a description of the role and nature of community input, from individuals and from groups, in all aspects of the network. Do not name or contact specific community-based organizations (CBOs) and non-government organizations (NGO) community advisors or organizations. Do provide the names, expertise/experience, roles and responsibilities of paid LOC staff who will be involved in community activities.

Describe how the LOC will work with other network LOCs to ensure efficient utilization of NIH resources to address cross-network hypotheses and endpoints. Specifically include plans to develop, implement and oversee clinical trials that address scientific questions of mutual interest. Coordination may consist of sharing network resources, including scientific, laboratory or statistical expertise and capabilities and/or CTU/CRS expertise and/or sites. Outline staff and/or infrastructure required to support inter-network negotiations, operations, and conflict resolution. Include decision trees and procedures for proposing cross-network trials, and identifying, selecting, and funding the CTUs/CRSs, SDMC and LC.

Provide a detailed plan to work with other LOCs, SDMCs, and LCs to identify and harmonize processes for working with CTUs and CRSs.

Discuss approaches and processes to ensure maximal use of the specimens collected during the course of NIH-supported clinical studies, both during the conduct of the study and after the study is completed.

Progress Report Publication List:

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

Letters of Support:

Provide appropriate letters of support limited to collaborators who have a significant role in the application. Note that letters establishing intra-network and cross-network collaborations are not necessary.

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 filename "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.

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.

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 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 does the overall proposed research agenda address the research priority areas of the FOA and does it address key clinical questions in HIV prevention research? Are the network structure and governance adequate to ensure that the LOC continues to respond to the most significant needs and opportunities in HIV prevention clinical research?

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 for the project, 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:

Do the PD/PI(s) and other key personnel have documented experience in directing clinical research projects of comparable size and scope required to address the objectives and scope of the network? Do they demonstrate appropriate expertise in protocol design, regulatory compliance, site selection, study implementation and coordination? Does the application identify investigators, study coordinators, project managers and staff experienced with operations for rapid implementation of early phase studies, as well as large multisite trials? Does/Do the PD(s)/PI(s) plan to devote sufficient effort to perform his/her role within the LOC?

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:

How well will the LOC structure allow for optimal innovation in HIV prevention clinical research?

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:

• Scientific Leadership
• Is there an appropriate and clear organizational structure for the LOC?
• Are there adequate lines of authority and strong, feasible governance plans for the LOC?
• Are plans to establish and utilize the EMC reasonable?
• Are contingency plans and ability to re-direct efforts in response to direction from the EMC clear?
• Are there appropriate plans for continuous refinement of the clinical research agenda?
• Are training and mentoring plans appropriate?
• Are the plans and approaches for evaluation and improvement of LOC performance appropriate?
• Does the LOC Quality Management Plan describe approaches to support regulatory compliance of clinical trials?
• Are there appropriate and feasible procedures for decision-making regarding protocol prioritization and development and to adjust, as needed?
• Are there appropriate plans to engage and receive input from the community?
• Does the application demonstrate leadership commitment and appropriate planning for successful cross-network collaboration and willingness to harmonize processes for better cross-network collaboration?
• Clinical Operations
• Are the management and communication plans adequate to manage, support and track protocol development and implementation?
• Are the proposed plans to coordinate scientific and fiscal responsibilities across the network adequate for the investigators to achieve the scientific goals of the network?
• Has the applicant proposed adequate plans for financial management of network resources?
• Has the applicant proposed adequate plans for soliciting, evaluating, awarding and managing subcontracts?
• Are there adequate plans to anticipate, track and adjust needs for each protocol regarding NIAID contract resources (e.g., clinical monitoring, regulatory, study products, etc.)?
• Are plans to apply project management principles to protocol development and implementation in place? Has the applicant proposed appropriate approaches to identify and assess clinical research site capacity?
• Are site performance expectations and plans to address poor site performance appropriate and clearly stated?
• Are the described approaches for implementation and completion of approved protocols both appropriate and adequate?

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 site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

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:

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

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Not Applicable

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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 on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the National Advisory 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 the application as well as 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).

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 Parts 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, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

PD(s)/PI(s) of the LOC, LC, and SDMC will have primary responsibility for the overall performance of the network, including, but not limited to the following within their individual awards:

• Identifying and implementing a clinical research agenda that addresses the NIAID scientific priorities and adapting the agenda over the period of the award.
• Establishing policies and procedures for collaboration with network elements and decision-making within the LOC to adapt to evolving research priorities over time.
• Maintaining close communication and coordination among the LOC, LC, SDMC, and affiliated CTU/CRS(s).
• Ensuring that the Quality Management Plans are implemented
• Convening or participating in meetings and teleconferences to facilitate collaboration and communication, to accomplish the objectives of the network.
• Overseeing all aspects of studies supported through the individual award, including study design, design modifications, conduct of the study, quality control and assurance, data analysis and interpretation, preparation of publications, dissemination of data, tools, and technologies, and collaboration with other investigators. PD(s)/PI(s) agrees to accept close coordination, cooperation, and participation of NIAID staff in those aspects of scientific and technical management of studies supported by this award as stated in these terms and conditions.
• Verifying that studies are conducted in compliance with 21 CFR Part 11 and ICHE6R2 guidelines.
• Adhering to NIAID DAIDS policy for the conduct of clinical trials.
• Managing involvement of industry or any other third party in studies supported by this award.
• Informing NIAID in the event that network grantee institutions enter into agreements that provide essential support (financial or in kind) to NIAID-sponsored clinical studies but are not actions as part of the network awards. The network grantee will inform NIAID of the terms of the agreement within 30 days of execution and provide updates in annual progress reports.
• Providing by-laws, policies and standard operating procedures to NIAID Program Staff within 90 days of issuance of an award, to include, at a minimum, the following:
• A Conflict of Interest (COI) Policy consistent with FDA regulations for Financial Disclosure by Clinical Investigators (21CFR54) in addition to requirements in the NIH Grants Policy Statement.
• Procedures to assure compliance with Division of AIDS Clinical Research Policies and Standard Procedures Documents and to ensure adequate protection of the rights and safety of subjects involved in the research.
• Detailed lines of authority and communication within the network and with NIAID program staff.
• Procedures to identify, qualify, and approve specific sites to address specific clinical research needs. In cases when clinical site capacity cannot be addressed within the existing CTU/CRS portfolio the LOC may identify, qualify, and approve protocol-specific sites as part of the LOC or associated with a CTU.
• Clinical Quality Management Plan, developed in accordance with DAIDS Requirements for Clinical Quality Management located within https://www.niaid.nih.gov/research/daids-clinical-site-implementation-operations and to be approved by DAIDS.
• Procedures for providing input to project protocol budgets and resource requirements, and tracking progress on protocols relative to award responsibilities, and communications to network and NIAID program staff to allow adjustment of the flow of resources to enable timely spending of funds and resources provided from outside the network awards.
• Determine the distribution of protocol funds, monitor expenditures relative to award responsibilities.
• Coordinate with NIAID and NIAID clinical research support programs to facilitate collection of site essential regulatory documents, activation of study sites, clinical site monitoring and quality assurance services, pharmacovigilance (SAE reporting) and safety oversight, in adherence with NIAID standards and processes.
• Coordinate with NIAID DAIDS Clinical Research Products Management Center (CRPMC) contractor to facilitate availability and distribution of study products.
• Ensuring the following are provided to NIAID Program Staff for each clinical trial:
• Project Management and communication plans
• Timelines and budgets
• Recruitment and Retention plan
• Clinical data management plan, including a process for sharing data with DAIDS and safety oversight group

Grantees are required to work closely with Clinical Monitors or Regulatory Auditors to ensure proper completion of all actions and steps associated with on-site monitoring or auditing, including review of corrective and preventative action plans when problems are detected.

If NIAID determines that a grantee fails to comply adequately with NIAID guidelines for the conduct of clinical trials, PD(s)/PI(s) will assure that the accrual of new patients to network protocols is immediately suspended and that the suspension remains in effect until notified that NIAID has conducted any required audit and the audit report or remedial action is accepted by NIAID. The PD(s)/PI(s) will assure that during the suspension period, no funds from this award are allowed for new accruals.

PD(s)/PI(s) of the Leadership and Operations Center (LOC) will have primary responsibility for the scientific leadership, administration and coordination of all network activities and the LOC, including, but not limited to:

• Convening and chairing the network's Executive Management Committee (EMC) to coordinate activities across the LOC, SDMC and LC and to coordinate activities with affiliated CTU/CRSs. The EMC is chaired by the LOC and includes the PDs/PIs of the LC and SDMC.
• Developing and implementing procedures for selecting and prioritizing research concepts
• Ensuring that protocol development is initiated only when:
• there is sufficient preclinical safety and supportive scientific data for the proposed study
• there is a commitment to supply sufficient study product, and financial resources are assured via an established system
• there is sufficient commitment and capacity within the network and CTU/CRSs to expeditiously complete protocol development, site approvals, accrual, conduct the study, analyze study data, and publish the research results
• there are transparent procedures in place for selecting members of a protocol team and selecting network-affiliated appropriate CTUs/CRSs
• there is a plan for assessing capacity of CRSs prior to site selection
• the protocol team is constituted with all the necessary expertise, including representation from the network Community Advisory Board and DAIDS
• the protocol chair has and commits adequate time throughout all phases of the protocol
• there are processes to ensure study reports are completed in a timely manner
• Ensuring that protocol implementation and oversight adhere to the following:
• established criteria for determining operational futility and when primary endpoints will not be reached within a pre-defined time boundary, prior to protocol initiation
• protocol approval by NIAID prior to protocol implementation resources to support the protocol such as study product, clinical site approvals for laboratories and pharmacies, and data management plans are in place
• mechanisms for monitoring study progress and participant safety, and provision of status reports to NIAID on an agreed upon schedule are in place
• previously outlined feasible follow-up plans, contingent upon study results, are in place
• results provided to study participants upon study un-blinding and to the community as soon as can be accomplished
• Ensuring that clinical trials are conducted in compliance with 21CFR Part 11 and ICHE6R2 guidelines
• Developing, training, and supporting network community advisory boards
• Implementing procedures for regular transparent assessment of CTU/CRS performance, which must include processes for the addition, reduction, expansion or elimination of network-affiliated CTUs/CRSs
• Determining, recommending and requesting protocol funds for the LOC, LC, SDMC and network-affiliated CTUs/CRSs and adjusting requested funds with protocol progress
• Meet administrative, oversight, and regulatory requirements by prompt submission of required information to NIAID including but are not limited to:
• Reports required by the IND sponsor, to fulfill regulatory requirements, compliant with federal regulations and NIAID procedures for clinical trials.
• Protocol documents; patient accrual and demographics; information concerning network-affiliated CTUs/CRSs; names, contact and additional information requested of all senior/key personnel; and training records
• PF reports as requested by NIAID
• As part of the annual non-competing RPPR, summarize all research accomplishments and provide detailed metrics on network performance and for the LOC, LC, SDMC and network-affiliated CTUs/CRSs. This annual report will also discuss activities, difficulties, corrective actions, and future directions with complete budget justifications.

PD(s)/PI(s) of the Laboratory Center (LC) will have the primary responsibility for the overall planning, execution and review of all laboratory center activities including, but not limited to:

• Aligning LC priorities with network research priorities as coordinated by the LOC
• Delegating responsibilities to lead investigators of the individual laboratories comprising the LC
• Ensuring that laboratories supported by the LC:
• Utilize necessary SOPs, permits, personnel, data management system and other resources to perform and report the results of laboratory assays to support network operations in timely manner to the required standards
• Domestic laboratories that perform any tests, including Clinical Laboratory Improvement Amendments (CLIA)-waived tests, on materials derived from the human body for providing information for the diagnosis, prevention or treatment of any disease or impairment, or the assessment of the health of human beings must be CLIA-accredited/College of American Pathologists (CAP) certified or equivalent.
• International laboratories performing endpoint testing to determine product efficacy that do not fall under CLIA must conduct operations under Good Clinical Laboratory Practice (GCLP) conditions, are subject to GCLP audits, and must receive a satisfactory evaluation when an audit is performed.
• Provide scientific expertise to the design and execution of clinical protocols, including evaluation of laboratory data
• Participate in network Quality Assurance/Quality Control (QA/QC) programs and NIAID External Quality Assurance (EQA) programs, proficiency testing and/or confirmatory retesting of samples when necessary to ensure the quality of performed tests.
• For clinical laboratories: Conduct tests for protocols being carried out under an Investigational New Drug Application (IND), New Drug Application (NDA) or Biological License Application (BLA) using FDA-approved tests and reagents. When not feasible, appropriate validation processes should be used with approval from the DAIDS Program Officer.
• Ensuring, wherever appropriate, that new assays are qualified or validated following current FDA guidelines on Biomedical Assay Validation and GCLP guidance.
• Engaging, where appropriate, non-network expert investigators and laboratories and other NIH-supported resources when identifying, evaluating and implementing new tests, reagents and instruments for clinical studies
• Transferring technology and sharing scientific information between LC specialty laboratories and CTU/CRS-affiliated laboratories
• Ensure security of any personally identifiable information associated with test specimens.
• Make specimens available for cross-trial and cross-network evaluation when required.
• Provide specimen access to non-network investigators when appropriate.

PD(s)/PI(s) of the Statistical and Data Management Center (SDMC) will have primary responsibility for the biostatistical and data management activities, including, but are not limited to:

• Under the coordination of the LOC, the SDMC has primary responsibility for compliance with 21 CFR and ICH guidelines as they relate to clinical trial data management at the SDMC, LC and CTU/CRS and statistical aspects of study design.
• Aligning SDMC priorities with network research priorities as coordinated by the LOC
• Ensuring that the SDMC has all the necessary SOPs, personnel, data management, statistical, and communications expertise and systems, and follows U.S. regulations, Good Documentation Practice, and relevant international guidelines to support network operations and meet NIAID requirements, to include:
• Ensuring timeliness, accuracy, confidentiality and integrity of data transferred within the network (i.e., laboratories, network-affiliated CRSs, SDMC).
• Ensuring timeliness, accuracy, confidentiality and integrity of data transferred between the Network and NIAID systems, NIH systems, and other federally required IT systems.
• Providing data to NIAID or a NIAID contractor upon request by NIAID to permit review of data as recorded on the case report forms (CRFs), electronic CRFs, or in the SDMC clinical trial management system.
• Providing closed and open reports required by data and safety monitoring committees; ensuring confidentiality of reports.
• Ensuring timely submission of data as required by the Food and Drug Administration (FDA) and other regulatory agencies.
• Interfacing, integrating or adapting the network’s information system(s) to be interoperable with NIAID systems.
• Adopting information systems or components specified by NIAID
• Collecting, storing and providing all data in accordance with Clinical Data Interchange Standards Consortium (C-DISC) requirements
• Collaborating with other DAIDS-affiliated SDMCs in the development of data elements that do not currently exist within C-DISC
• Serving as primary reporter for electronic reporting and updates about network studies to NIH in the eRA Humans Subjects System (HSS)
• Working cooperatively with counterparts from other NIH-supported clinical trials networks to conduct collaborative research projects and ensure capability for cross-protocol and cross-network data analysis. This may include:
• Establishment of standard data interfaces and common data elements, protocol status definitions, endpoint verification, formats for data collection, and site identification systems;
• Creation and exportation of datasets for meta and epidemiologic analysis
• Adaptation of current database systems and structures to accommodate multi-network collaboration and data exchange
• Sharing data publicly through NIAID-specified portals (e.g., ImmPort, ImmuneSpace), as appropriate and consistent with achieving the goals of the program. The PD/PI will establish procedures within the network to ensure that all members of that network conform to the data sharing and other resource-sharing plans.

Each network will have the responsibility to collaborate and promote inter-network interactions, including but not limited to:

Coordinating with other NIAID- and NIH-supported clinical trials networks to:

• Support observance of and compliance with federal regulations and international standards for clinical studies
• Avoid redundancy and ensure harmonization
• Establish performance measures for evaluating the efficiency and effectiveness of the LOC, LC, SDMC, and network-affiliated CTUs/CRSs
• Standardize and share training for common needs
• Develop cross-network communication strategies, including community participation

NIH staff 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:
• Provide specific guidance on expectations for clinical studies and clinical trials.
• Ensure that network research efforts are consistent with NIAID priorities for HIV clinical research and complement other NIH and NIAID programs;
• Facilitate coordination among the NIAID- and other NIH-supported clinical trials networks and research groups, clinical research support programs, and other U.S. Government agencies, promoting collaborations and facilitating information exchange;
• Review and accept processes for identifying, qualifying, and approving protocol-specific sites to address specific network needs after award;
• Serve as members of protocol teams;
• Monitoring progress of grant awards with regard to protocol development, implementation, and study conduct, and making adjustments as necessary;
• Participate in meetings, training activities, and conference calls;
• Serve as resources for scientific and policy information;
• Provide information regarding promising new agents, strategies, and developments when appropriate;
• Identify scientific gaps and organize meetings to facilitate exchange of scientific and regulatory information, including during network meetings;
• Periodically conduct an independent review of the constituent parts of the network for reliability and compliance with clinical and regulatory requirements including third party audits;
• Coordinate contract resources that facilitate the provision of support services for clinical trials;
• Participate on scientific committees as a voting member;
• 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.
• Clinical Trials Agreements. NIAID will lead the negotiation of Clinical Trials Agreements (CTAs) and serve as the liaison with pharmaceutical companies (or other providers of investigational agents).
• Trial Sponsorship. NIAID will have the option to independently file an IND on investigational agents or an IDE on investigational devices evaluated in NIAID-supported clinical studies. NIAID will advise the investigators on the specific regulatory requirements for IND/IDE sponsorship. In situations where NIAID is the IND sponsor, NIAID through its contractors will also assemble, review, and submit the required regulatory documents to the FDA. When holding an IND or IDE, NIAID has responsibility for the data management and reporting of safety information in accordance with FDA requirements and preferences. In order to provide for consistent reporting of serious adverse experiences across the NIAID-supported clinical trial networks, NIAID will provide current policies and procedures that govern the reporting of adverse events in NIAID-supported trials.
• Pharmaceutical Support. For studies in which NIAID is the IND or IDE sponsor, IC staff and/or contractors will provide consultation on study treatment-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.
• Trial Monitoring. NIAID will oversee an external clinical site monitoring contract that evaluates GCP, regulatory compliance, protocol implementation, internal quality assurance, and test article accountability at the clinical research sites for clinical trials conducted under IND/IDE. The monitoring contractor, with or without accompanying NIAID staff, will visit the clinical research sites periodically to review selected protocols, provide training on general protocol conduct, review internal QA/QC plans, and audit pharmacies. When NIAID is not the regulatory sponsor, clinical monitoring support is provided based on a case-by-case determination.
• Training. NIAID staff will provide a variety of training activities to appropriate network personnel to help the network ensure that consistent standards for protection of human subjects and clinical trial conduct and documentation are achieved across the NIAID-supported clinical trials networks. Training areas include, but are not limited to, regulatory requirements, GCP, adverse event reporting, human subject protections, informed consent, and NIAID and NIH policies and procedures.
• Protocol approval. NIAID will review and provide approval for all protocols. NIAID or designee will return comments and recommendations to the network after review. The network must address in writing all safety, regulatory, ethical, and conflict of interest concerns raised by NIAID to the satisfaction of NIAID before participant enrollment can begin. If a protocol is disapproved, NIAID will not provide investigational products or permit expenditure of NIH funds for the proposed investigation. When a protocol is not initiated within twelve months of NIAID approval, re-review and approval by NIAID will be required.
• Safety Monitoring. NIAID participates in development of appropriate safety monitoring plans for all planned clinical trials, and must approve the plan for all trials involving investigational drugs, devices, 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 experience with study products and may require review by an Independent Safety Monitor, 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. Medical Officers will be responsible for the disposition of Serious Adverse Events. Approval of the final monitoring plan, including the composition of the review committee, by NIAID is required prior to study initiation. NIAID independently supports Data and Safety Monitoring Boards (DSMBs) that oversee Phase IIb/III and other select clinical trials at the discretion of NIAID.
• Protocol Termination. NIAID reserves the right to terminate or curtail a clinical study for any of the following reasons:
• risk to subject safety
• the scientific question is no longer relevant, or the objectives will not be met (i.e., slow accrual)
• failure to comply with GCP, U.S. Federal regulations, or Terms and Conditions of Award
• occurrence of unforeseen drug safety issues or data from preclinical studies indicate a presence of unanticipated toxicity
• risks that cannot be adequately quantified
• ethical concerns raised by the community or medical care/health care authorities
• failure to remedy deficiencies identified through site monitoring
• substandard data
• reaching a major study endpoint substantially before schedule with persuasive statistical significance

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/IDE sponsor. NIAID may request from the network 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 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.

Areas of Joint Responsibility include:

• Research Plans. Implementing, monitoring, and updating the clinical research priorities for the network to ensure consistency and relevance
• Research Activities. Reviewing the network's research activities and goals on an agreed upon schedule (but no less than once every year).
• Protocol Development. The LOC will assemble and manage protocol teams, but NIAID staff and support contractors, as required, will participate in these teams.
• Oversight of Clinical Trials. On an ongoing basis, the LOC, LC, 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 GCP and data quality and integrity.
• Performance Assessment. NIAID, in conjunction with the EMC will assess the performance of the LOC, SDMC, and LC and CTUs/CRSs in an ongoing manner. The EMC will develop an evaluation plan with defined goals and measurable objectives linked to specific performance metrics and include remedial actions for sites failing to meet acceptable standards. Clinical research sites that fail to meet performance standards may be subject to withdrawal of funding.
• Community Partners. Representatives of network 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
• Enhance intra- and inter-network community communications and input
• Identify needs for training and support of local and network community advisory boards
• External Advisors. NIAID may seek evaluation, advice and recommendation concerning ongoing and planned research activities of the network from external advisors. Advisors will not include key personnel or collaborators of the key personnel of any of the awardees. Network investigators will participate in these evaluations with attendance supported through the LOC budget and will provide written materials and oral presentations regarding the status of ongoing research activities, future (including proposed new research activities/investigators), and plans to curtail, discontinue and/or modify current research activities.

Dispute Resolution:

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

When multiple years are involved, awardees will be required to submit the 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]

Michael Gilbreath, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4793
Email: [email protected]

Naana Cleland, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4779
Email: [email protected]

Sonia Lee, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-4783
Email: [email protected]

Richard A. Jenkins, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-443-1923
Email: [email protected]

Michael Stirratt, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3875
Email: [email protected]

Dharmendar Rathore, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5058
Email: [email protected]

Jenny Greer
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2949
Email: [email protected]

Bryan Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

Pam Fleming
National Institute on Drug Abuse (NIDA)
Telephone: 301-480-1159
Email: [email protected]

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
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 .