Table 1. Key uncertainties and questions about the use of clinical and translational pharmacology, biomarkers, and microbiology to advance TB treatments that were addressed at the WHO-sponsored workshop, advances in clinical trial design for development of new TB treatments.

(Adapted from [15]).

Topic Area	Question
Clinical Pharmacology	What is the importance of understanding PK-PD relationships by phase of regimen development?
Pharmacometrics	How does quantitative modeling and simulation integrate PK and microbiology-based PD measures (e.g., MIC, bacterial burden as predictive covariates of treatment response) to inform drug development decision-making, especially in later stages of regimen evaluation?
Preclinical/Translational Pharmacology	Can dynamic experiment-level in vitro assessments (i.e., HFS-TB) be integrated with patient-level bacteriological data to improve quantitative clinical PK-PD predictions and streamline model development?
Biomarkers	What would be the most efficient framework for bacteriologically based biomarker identification and characterization in clinical trials to enable integration in modeling and simulation-based analyses?
Bacteriology	Should quantitative PK-PD models describing relevant bacteriologically based covariates be used to guide dose finding and dose optimization in key populations during early development?
Drug Development	How do we make use of PK-PD across clinical development phases to identify pharmacology-guided drug regimens?

Abbreviations: HFS-TB, hollow-fiber in vitro pharmacodynamic system for assessing TB drugs; MIC, minimum inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; TB, tuberculosis