Phase 0/microdosing approaches: time for mainstream application in drug development?
Tal Burt, Graeme Young, Wooin Lee, Hiroyuki Kusuhara, Oliver Langer, Malcolm Rowland, Yuichi Sugiyama
Nature Reviews Drug Discovery September 8, 2020 DOI: 10.1038/s41573-020-0080-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Microdosing |
| Keywords | Mainstream Drug development Pharmacology |
| Citations | 101 |
| Key findings | Phase 0 approaches can improve preclinical candidate selection and enable safer, cheaper, quicker, and more informed developmental decisions. |
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.