FIG 1.

Standardized workflow for the systematic investigation of parasite-host-drug dynamics throughout the (pre)clinical antimalarial development process. (a) Mechanistic models of parasite growth are calibrated to extensive undisturbed parasite growth (control) data in murine and human infection experiments on a population (mouse) or individual (human) level. Combined with models of drug concentration (PK) over time, they are used to calibrate to treatment data over multiple doses and drugs. Models were selected for further analysis based on appropriate goodness-of-fit measures and assessment of biological plausibility. (b) Model simulation over multiple drugs and doses facilitates the comparison of the parasite reduction rate over all experimental systems. Subsequent sensitivity analysis allows the identification of parasite, host, or drug dynamics as the drivers of experimental outcomes.