Clinical proof-of-concept trials crucially inform major resource deployment decisions. This paper discusses several mechanisms for enhancing their rigour and efficiency. The importance of careful consideration when using a surrogate endpoint is illustrated; situational effectiveness of run-in patient enrichment is explored; a versatile tool is introduced to ensure a strong pharmacological underpinning; the benefits of dose-titration are revealed by simulation; and the importance of adequately scheduled observations is shown. The general process of model-based trial design and analysis is described and several examples demonstrate the value in historical data, simulation-guided design, model-based analysis and trial adaptation informed by interim analysis.

临床概念验证试验可为重要的资源部署决策提供至关重要的信息。本文讨论了提高其严谨性和效率的几种机制。说明了使用替代端点时应仔细考虑的重要性；探索磨合患者充实的情境有效性；引入了一种通用工具，以确保强大的药理基础；模拟显示了剂量滴定的好处；并显示了适当安排的观察的重要性。描述了基于模型的试验设计和分析的一般过程，并举例说明了历史数据，模拟指导设计，基于模型的分析以及通过临时分析提供信息的试验适应性的价值。