The purpose of this Funding Opportunity Announcement (FOA) is to solicit applications to form a Leadership Group for an Infectious Diseases Clinical Research Consortium, hereafter referred to as the Leadership Group (LG), to support the planning and implementation of clinical research that addresses the scientific priorities of NIAID in evaluating vaccines, other preventive biologics, therapeutics, diagnostics, including prognostic and predictive markers, and devices for the treatment and prevention of infectious diseases. A companion FOA solicits Vaccine and Treatment Evaluation Units (VTEUs), which will provide the scientific, administrative expertise and infrastructure to implement the clinical research. Although the scientific focus will be on malaria/neglected tropical diseases, sexually transmitted infections, respiratory infections, and enteric diseases, the LG and VTEUs will work collaboratively to monitor, identify and adjust research priorities based on potential emerging infectious diseases.
For over 50 years, NIAID has supported the Vaccine and Treatment Evaluation Units (VTEUs), which have performed high-quality clinical research under Investigational New Drug (IND) status to evaluate the safety and efficacy of vaccines and other countermeasures for infectious diseases. Moving forward, the VTEUs will work in tandem with the LG to enhance integration and efficiency in operations, increase collaborations, review and prioritize concepts, plan for protocol implementation, and evaluate ongoing studies. Together, the LG and VTEU programs will foster collaborative team science approaches to address NIAID priorities, such as universal influenza vaccination. Moreover, the LG will assemble Expert Working Groups from specific infectious diseases areas who will prioritize the clinical research to be implemented using their expertise and the current public health environment as reference.
For this FOA, NIAID scientific priority areas include clinical research and Phase I-IV clinical trials for vaccines and other biologics, therapeutics, diagnostics and devices targeting a wide array of infectious diseases, including newly emerging infectious diseases. The LG will collaborate with NIAID to identify and implement clinical research studies and clinical trials that will impact the prevention, diagnosis and treatment of a wide array of infectious diseases. The highest priority for clinical research will be the top infectious disease(s) threats identified by US and international expert bodies, such as the Centers for Disease Control and Prevention and the World Health Organization. A unique feature of the LG is the formation of multiple scientific working groups to provide expert input on the priority research foci of NIAID, such as:
- Malaria/neglected tropical diseases
- Sexually transmitted infections
- Respiratory infections, particularly influenza
- Enteric diseases
- Emerging infectious diseases and other infectious disease considerations
Examples of research activities within the priority research areas include, but are not limited to:
- Evaluation of vaccine and therapeutic candidates
- Pharmacokinetic assessments in Phase 1 first-in-human studies and population pharmacokinetic studies
- Evaluation of sexually transmitted infection diagnostic tools
- Controlled human infection models
- Rapid response to future disease outbreaks, (for example, emerging diseases: e.g. Ebola, chikungunya, and Zika)
- Isolation and characterization of circulating pathogens
- Evaluating reagents and tools for newly emerging diseases
The LG is organized to capitalize on the multiple elements of the program to address current research priorities and develop capacity to respond rapidly to newly emerging disease threats. The structure of the LG includes a Leadership Operations Center (LOC), a Clinical Operations Unit (COU), a Laboratory Operations Unit (LOU), a Statistical Support Unit (SSU) and the Expert Working Groups (EWG). The activities and synergies of the LG will support the large-scale, complex Infectious Diseases Clinical Research Consortium (IDCRC), composed of the LG, VTEUs, NIAID, and NIAID-supported research resources. Collectively, the IDCRC will carry out the clinical research priorities of NIAID.
Applications must contain the following LG Program Elements: Leadership Operations Center (LOC), Clinical Operations Unit (COU), Laboratory Operations Unit (LOU), Statistical Support Unit (SSU), in addition to an application Overview. Applications lacking one or more LG Program Element will be considered incomplete and will not be reviewed.
Leadership Operations Center (LOC)
The LOC will be responsible for overall administrative leadership for the LG, as well as oversight and evaluation of all LG activities, including refining the research agenda, prioritizing research concepts, and ensuring timely publication and communication of results. The LOC is also responsible for the following:
- Governance. Integral to the success of the LOC 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 resource distribution policies. The LOC may establish internal committees to achieve the work of the LG.
- Research Priorities. The LOC works closely with NIAID Program Staff to ensure the research agenda is consistent with NIAID’s infectious diseases research priorities. The LOC will involve the Expert Working Groups in the prioritization and implementation of the NIAID infectious diseases clinical research agenda.
- Innovation. The LOC explores innovative types of infectious disease countermeasures, study/trial designs, approaches to public-private partnerships, and statistical techniques that will have a broad impact on infectious diseases clinical research.
- Mentoring. The LOC identifies clinical research experience opportunities for junior investigators. This may take the form of small clinical research projects, classroom training in clinical research and statistical analysis, participation in LG committees, participation as junior investigators on studies and trials, and exposure to other aspects of clinical research on infectious diseases.
- Monitoring and Evaluation. The LOC develops and incorporates policies, methods and approaches for monitoring implementation of clinical research conducted by the VTEUs and evaluates the operational performance of the overall LG and each element within the LG.
- Quality Management. The LOC develops strategies for assuring quality management, to ensure that risk assessment and mitigation strategies are an integral part of all research activities within the LG. These strategies will complement quality management systems and processes established by NIAID.
- Collaborative Responsibilities. The LOC seeks out opportunities for collaboration with other NIH-supported clinical networks, and other Federal and private sector clinical research programs. Such collaborations and interactions are essential for the development and implementation of a comprehensive research agenda that utilizes the strengths, experience and expertise of the various collaborating organizations. Sharing of expertise, resources and procedures is expected in key areas, including: harmonization of laboratory resources and specimen management and harmonization of common data elements and data entry interfaces.
- Expert Working Groups (EWG). Multiple groups of scientific experts with expertise in discrete areas of infectious diseases research serve on area-specific working groups to provide advice and recommendations to the LG. The LG will use this information to monitor and prioritize clinical research undertaken by the LG as a function of public health relevancy and need. Areas of working group expertise might include, for example, clinical trial design, vaccine evaluation, immunology, pharmacokinetics, and leadership in priority scientific fields. In addition, experts may be included in specific targeted populations such as pediatrics, geriatrics, maternal/fetal health, etc., and international experts knowledgeable in the field of study and the location of study execution based on geographical reference. In the event of a public health emergency, ad hoc expert working groups could be formed to address specific scientific expertise to assist with protocol development and implementation. The working groups develop protocol synopses outlining the key aspects of planned protocols, review and prioritize concepts for clinical research proposed by the LOC, and plan for clinical research implementation by the VTEUs. The expectations are that working groups are constituted and prepare protocol synopses within the first six months of award. Note: The working groups are expected to consist of VTEU PD(s)/PI(s) or their designees and other experts who are recognized leaders in their specific scientific fields. Working group(s) members should not be named or recruited prior to award.
Clinical Operations Unit (COU)
The COU provides operational support, management, and oversight for the LG’s clinical research. This requires close coordination with the various units within the LG, the VTEUs as the research implementation sites, NIAID staff, and NIAID-provided research support programs. The COU provides leadership on protocol development and implementation planning and is responsible for site selection, qualification, and management of protocol-specific sites. A major activity of the COU will be the establishment of efficient processes for identifying, qualifying, and approving protocol-specific sites to address specific clinical research needs. The COU manages and oversees protocol teams for all LG activities, and establishes efficient systems for resource distribution and reallocation in response to evolving priorities identified by the LOC. Finally, the COU provides specialized training for clinical trials, applicable laboratory procedures and data management for LG staff in support of LG activities. The COU is responsible for the following activities:
- Management. The COU manages, oversees and coordinates long-term and day-to-day activities associated with LG clinical research, including, for example: development of project plans and establishment of realistic milestones and timelines; ongoing evaluation and adjustments to timelines; and implementation of contingency plans. The COU develops standard operating procedures (SOPs), budgets, and communication plans.
- Protocol Development. The COU coordinates activities required to advance protocol synopses through to full protocols and prepares additional protocol-specific documents (e.g. Manual of Procedures (MOP), Statistical Analysis Plans (SAP), etc.).
- Budget Development. The COU prepares budgets for protocol implementation.
- Clinical sites. The COU works with the VTEUs and NIAID to identify the optimal balance of sites for implementation of the clinical research, based on the diverse nature of LG clinical research needs and required patient populations. The COU will evaluate study and trial conduct at the clinical sites. The LG clinical research may be implemented at performance sites within the VTEUs or subcontracted to protocol-specific domestic or international clinical sites by the LG. The VTEUs are considered the fixed sites funded through cooperative agreements with NIAID for continuous operation in implementing clinical research developed through LG activities. At times of specific need, the LG will need to identify and incorporate protocol-specific sites to meet goals or recruitment needs of the supported research. Protocol specific sites are clinical research sites opened for capacity to implement specific protocols when eligibility criteria cannot be met by fixed sites alone, or when surge capacity is required to respond in a high priority research area.
Laboratory Operations Unit (LOU)
The LOU leads the development, implementation and evaluation of the laboratory research that is essential to the successful execution of the LG research agenda. The LOU manages and oversees relevant laboratory services, including any necessary pharmacokinetics (PK) services, bioanalyses, and specimen characterization; laboratory quality management programs; the monitoring and evaluation of all specialized laboratories under the purview of the LG; sharing of specimens outside the LG, as necessary; and providing adequate storage facilities necessary to accomplish the LG’s clinical research agenda. The LOU leadership fosters collaboration and harmonization of laboratory activities within the LG and the VTEU-identified laboratories.
Statistical Support Unit (SSU)
- For trials under a NIAID held IND, the SSU provides: leadership and services for biostatistics, study design, interpretation and publication of results. This includes performing the role of blinded (masked) biostatistician with regard to Safety Monitoring Committees (SMC) and Data and Safety Monitoring Boards (DSMB) activities in randomized controlled trials with blinded (masked) data, assisting NIAID and NIAID-sponsored programs in responding to regulatory inquiries regarding clinical trial design and may include analysis during a study. The SSU collaborates with other NIAID-sponsored programs as necessary.
- For non NIAID held IND trials, the SSU provides: leadership, services and oversight for biostatistics, study design, analysis, interpretation and publication of results, clinical and laboratory data management systems compliant with all current applicable Federal regulations (https://www.ecfr.gov/cgi-bin/text-idx?SID=3ee286332416f26a91d9e6d786a604ab&mc=true&tpl=/ecfrbrowse/Title21/21tab_02.tpl ) and globally accepted standards, such as: International Council on Harmonization (ICH) E2, E3, E6, M5, MedDRA Terminology (http://www.ich.org/products/guidelines.html); World Health Organization Drug Dictionary (http://apps.who.int/medicinedocs/en/d/Js4953e/4.html; and Clinical Data Interchange Standards Consortium (CDISC) (https://www.cdisc.org/). The systems should be capable of interfacing with other systems. The SSU collaborates with other NIAID sponsored programs as necessary and provides systems training.
- For non-IND trials, the SSU provides: leadership, services and oversight for biostatistics, study design, analysis, interpretation, and publication of results, clinical and laboratory data management systems, to include randomization, and training to ensure accurate, complete, and high-quality data. The systems should be capable of interfacing with other systems.
- The SSU is responsible for standardizing and harmonizing statistics and data management activities, as applicable, within the IDCRC and coordinating with other NIAID sponsored programs as necessary.
Additional resources provided by NIAID:
- Safety Oversight Committees. NIAID oversees the safety of all participants in clinical trials funded by NIAID. NIAID monitors Phase II, Phase III and Phase IV multicenter, randomized clinical trials primarily through DSMBs. NIAID monitors Phase I and small Phase II clinical trials primarily through SMCs in conjunction with Independent Safety Monitors (ISMs) (see https://www.niaid.nih.gov/research/safety-oversight-clinical-research). For the LG, NIAID will provide access to the services needed to provide clinical trials oversight.
- Other Support Services. Responsibility for Investigational New Drug (IND) sponsorship will be determined on a case-by-case basis and may rest with either the Program Directors (PDs)/Principal Investigators (PIs) or with NIAID — NIAID will make this determination. NIAID will provide additional support services for LG trials that must be conducted under an IND or Investigational Device Exemption (IDE). These services may include: domestic regulatory sponsorship (Regulatory Support Contract), data management and statistical support (SDCC), management of clinical agents and specimens (Clinical Material Services Contract, and clinical site monitoring (Clinical Research Operations and Management Support Contract). Each study will be evaluated for the need for an IND/IDE by NIAID and support services to be provided will be determined on an individual study basis. For clinical trials that do not require an IND/IDE, the LG will provide all support services other than safety oversight. For clinical studies that do not meet the NIH definition of a clinical trial, the LG will provide all resources and expertise necessary for the conduct of the study.
- NIAID will provide a variety of training activities to appropriate LG personnel to help the LG 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.
Deadline: January 15, 2019 (letters of intent due 30 days prior to the deadline)
Filed Under: Funding Opportunities