Advancing the development of new tuberculosis treatment regimens: The essential role of translational and clinical pharmacology and microbiology

Summary points

• Translational and clinical pharmacology are the state-of-the-art tools used by drug developers to efficiently move compounds and regimens through all drug development phases. Tuberculosis drug and regimen development, though, has traditionally underutilized these modern, model-based drug development approaches, despite the urgent need to understand major pharmacological aspects not only of the new candidates but also of existing drugs.
• Translational platforms that include drug combinations are critical and should encompass data from multiple preclinical drug development tools (in vitro and in vivo models) to select the best regimens to be moved forward into clinical development.
• Quantitative pharmacokinetic (PK)–pharmacodynamic (PD) approaches should be incorporated into all phases of drug development and be used for selection of optimal dose and schedule, assessment of drug–drug interactions, and dose determination in key populations including pregnant women, children, and people living with HIV. Quantitative pharmacology models should further be utilized for clinical trial design using clinical trial simulations.
• Microbiology determinants such as precisely assessed minimum inhibitory concentrations (MICs) as well as quantitative longitudinal cultures integrated with PK-PD assessment will substantially inform and enhance all phases of drug development.
• Commitment of all stakeholders, data sharing, and resource investment are required for development and utilization of these tools, which are necessary for successful TB regimen development.