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.

阶段0的方法（包括微量给药）在被称为探索性临床试验的首次人类研究中评估新药的亚治疗暴露。最新进展将第0阶段的益处扩展到了药代动力学评估之外，包括对作用机理和药效学的理解。阶段0方法有可能改善临床前候选者的选择，并实现更安全，更便宜，更快和更明智的开发决策。在这里，我们讨论了阶段0的方法和应用，突出了它们相对于传统策略的优势，并解决了与外推和发展时间表有关的问题。尽管仍然存在挑战，但我们建议至少在大多数药物开发场景中考虑使用阶段0方法。