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Phase-0/Microdosing Network. Phase-0Microdosing.org, New York, NY, USA.
Nat Rev Drug Discov. 2020 Nov;19(11):801-818. doi: 10.1038/s41573-020-0080-x. Epub 2020 Sep 8.
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.
0 期研究方法——包括微剂量——在被称为探索性临床试验的首次人体研究中评估新药的亚治疗暴露。最近的进展将 0 期研究的益处从药代动力学评估扩展到包括对作用机制和药效动力学的理解。0 期研究方法有可能改善临床前候选药物的选择，并使开发决策更安全、更经济、更快、更明智。在这里，我们讨论了 0 期研究方法及其应用，强调了它们相对于传统策略的优势，并解决了与外推和开发时间有关的问题。尽管仍存在挑战，但我们建议至少在大多数药物开发情况下考虑应用 0 期研究方法。
