Phase 0/microdosing approaches: time for mainstream application in drug development?
- 8 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Reviews Drug Discovery
- Vol. 19 (11), 801-818
- https://doi.org/10.1038/s41573-020-0080-x
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.Keywords
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