The product of independent beta probabilities escalation (PIPE) design for dual-agent phase I dose-escalation trials is a Bayesian model-free approach for identifying multiple maximum tolerated dose combinations of novel combination therapies. Despite only being published in 2015, the PIPE design has been implemented in at least two oncology trials. However, these trials require patients to have completed follow-up before clinicians can make dose-escalation decisions. For trials of radiotherapy or advanced therapeutics, this may lead to impractically long trial durations due to late-onset treatment-related toxicities. In this paper, we extend the PIPE design to use censored time-to-event (TITE) toxicity outcomes for making dose escalation decisions. We show via comprehensive simulation studies and sensitivity analyses that trial duration can be reduced by up to 35%, particularly when recruitment is faster than expected, without compromising on other operating characteristics.

中文翻译：

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使用审查的毒性时间数据进行联合治疗 I 期试验的贝叶斯无模型方法。


双药 I 期剂量递增试验的独立 β 概率递增 (PIPE) 设计的产物是一种贝叶斯无模型方法，用于识别新型联合疗法的多种最大耐受剂量组合。尽管 PIPE 设计于 2015 年才发表，但已在至少两项肿瘤学试验中实施。然而，这些试验要求患者完成随访后临床医生才能做出剂量递增的决定。对于放射疗法或先进疗法的试验，由于迟发性治疗相关的毒性，这可能会导致试验持续时间过长，不切实际。在本文中，我们扩展了 PIPE 设计，以使用经过审查的事件时间 (TITE) 毒性结果来做出剂量递增决策。我们通过全面的模拟研究和敏感性分析表明，试验持续时间最多可缩短 35%，特别是当招募速度快于预期时，且不会影响其他操作特性。