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Review
. 2020 Nov;19(11):801-818.
doi: 10.1038/s41573-020-0080-x. Epub 2020 Sep 8.

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

Tal Burt  1   2 , Graeme Young  3 , Wooin Lee  4 , Hiroyuki Kusuhara  5 , Oliver Langer  6   7 , Malcolm Rowland  8 , Yuichi Sugiyama  9
Affiliations
Review

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

Tal Burt et al. Nat Rev Drug Discov. 2020 Nov.

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.

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