Objectives in Phase II drug combination studies are to estimate the efficacy response surface for the combination of doses of different drugs and to select the most efficient combination for the final Phase III clinical trial. One problem is to find an optimal design that allocates subjects to the dose-combinations which will maximize the information obtained in the trial. Adaptive designs help in these situations to ensure high efficiency of the study design. We are using a binary efficacy endpoint and consider the practical situation when the timing of the endpoint assessment period on the subject level is considerably longer relative to the inter-arrival time of subjects. This poses implementation challenges for the adaptive design. A solution to the adaptive design problem by using time-to-event models as longitudinal model will be presented.

中文翻译：

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由响应的纵向模型通知的药物组合的自适应设计

II 期药物组合研究的目标是估计不同药物剂量组合的疗效响应面，并为最终的 III 期临床试验选择最有效的组合。一个问题是找到一种最佳设计，将受试者分配到剂量组合，这将使试验中获得的信息最大化。在这些情况下，自适应设计有助于确保研究设计的高效率。我们正在使用二元疗效终点，并考虑当受试者级别的终点评估期的时间相对于受试者的到达间隔时间相当长时的实际情况。这给自适应设计带来了实施挑战。将提出使用时间到事件模型作为纵向模型来解决自适应设计问题。