Phase 0/microdosing approaches: time for mainstream application in drug development?

Phase 0 approaches, including microdosing, are early-stage clinical trials that test very low, subtherapeutic doses of new drugs in humans to gather safety and pharmacological data before larger studies. Traditionally used to assess pharmacokinetics, these methods now also help understand a drug's mechanism of action and pharmacodynamics. Phase 0 trials can improve the selection of drug candidates for further development, making the process safer, cheaper, quicker, and more informed. While challenges like extrapolating results to therapeutic doses and managing development timelines remain, the authors suggest that phase 0 approaches should be considered for most drug development scenarios.

Study at a glance

Abstract

Phase 0 approaches - which include microdosing - evaluate subtherapeutic exposures of new drugs in first-in-human studies known as exploratory clinical trials. Recent progress extends phase 0 benefits beyond assessment of pharmacokinetics to include understanding of mechanism of action and pharmacodynamics. Phase 0 approaches have the potential to improve preclinical candidate selection and enable safer, cheaper, quicker and more informed developmental decisions. Here, we discuss phase 0 methods and applications, highlight their advantages over traditional strategies and address concerns related to extrapolation and developmental timelines. Although challenges remain, we propose that phase 0 approaches be at least considered for application in most drug development scenarios.