Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as immunotherapies and targeted treatments, often exhibit delayed effects that challenge traditional trial designs. These delayed effects violate the proportional hazards assumption, which underpins standard statistical methods like the Cox proportional hazards model and the log-rank test. Careful planning is essential to ensure trials are appropriately designed to account for the timing and magnitude of these effects. Without this planning, interim analyses may lead to premature trial termination if the treatment effect is underestimated early in the study. We present an adaptive trial design framework that incorporates prior distributions, elicited from experts, for delayed treatment effects. By addressing the uncertainty surrounding delayed treatment effects, our approach enhances trial efficiency and robustness, minimizing the risk of premature termination and improving the detection of treatment benefits over time. We present an example illustrating how interim analyses, informed by prior distributions, can guide early stopping decisions. To facilitate the implementation of our framework, we have developed free, open-source software that enables researchers to integrate prior distributions into trial planning and decision-making. This software provides a flexible, accessible tool for designing trials that more accurately evaluate modern therapies through adaptive trial designs.

翻译：以时间至事件结局（如总生存期（OS）或无进展生存期（PFS））为终点的临床试验，是评估新疗法（尤其在免疫肿瘤学中）的基础。然而，现代疗法（如免疫疗法和靶向治疗）常表现出延迟效应，这对传统试验设计构成挑战。这些延迟效应违背了支持标准统计方法（如Cox比例风险模型和对数秩检验）的比例风险假设。为确保试验设计恰当地考虑这些效应的时间与幅度，周密的规划至关重要。若无此规划，若研究早期低估治疗效果，期中分析可能导致试验过早终止。我们提出一个自适应试验设计框架，该框架纳入从专家处诱发的关于延迟治疗效应的先验分布。通过解决延迟治疗效应相关的不确定性，我们的方法提升了试验效率与稳健性，降低了过早终止的风险，并随时间推移改善了治疗获益的检测能力。我们通过一个实例展示，基于先验分布指导的期中分析如何辅助早期停止决策。为促进我们框架的实施，我们开发了免费的开源软件，使研究者能够将先验分布整合至试验规划与决策中。该软件提供了一个灵活、易用的工具，通过自适应试验设计更准确地评估现代疗法。