An expert meeting was held in 2012 to define potential pathways and explore new paradigms to accelerate the development of new antibacterial drugs that would address unmet medical need and to discuss issues in ABDD clinical trial design, including endpoints and operational efficiencies specific to the development of antibacterial drugs for treating patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). Participants agreed that it is critical for all stakeholders to work together to characterize novel research models and seek alternatives to traditional superiority trials in ABDD. The following paragraphs summarize suggestions made by the experts to address particular trial issues in ABDD.
To address challenges with enrollment into ABDD trials, experts suggested the following: performing studies in geographic areas where the pathogen is endemic, or where there is a greater likelihood of encountering serious infections; improving rapid diagnostics; and creating large networks of research sites to ensure consistency and efficiency in the execution of innovative trials. The latter may also facilitate collaboration and improve coordination for a more rapid response to newly identified outbreaks of resistant pathogens. Issues with clinical trial design and data analyses may be simplified by including a development/approval pathway using a smaller clinical trial database, using well-defined and reliable efficacy endpoints, and identifying suitable control groups for various study design scenarios. Potential solutions in ABDD to meet the unmet need for antibacterial drugs may rely on accelerated approval, heightened post-marketing surveillance, collaboration among stakeholders, and the efforts of those involved in the clinical trials ecosystem to establish a new model of ABDD.
At the expert meeting, attendees also discussed unmet need in HABP/VABP. They explored topics such as the feasibility of endpoints, biomarkers, and other surrogates in HABP/VABP trials; collaborative efforts for data sharing/mining across the available clinical databases; and the need for additional education and potential acceptance of both accelerated approval and use of alternative endpoints in ABDD. Experts also discussed potential solutions to improving the operational efficiency and feasibility of HABP/VABP trials. Briefly, streamlining strategies were discussed as well as plain-language informed consent forms, site pre-approval for enrollment of future studies, simplified data collection, promotion of FDA guidances, clearer public communication, and use of organized research groups (e.g., AIDS Clinical Trial Group) as models. HABP/VABP trial-specific results are presented and discussed in more detail in the Streamlining HABP/VABP Trials Project.