Precision medicine has led to a paradigm shift allowing the development of targeted drugs that are agnostic to the tumor location. In this context, basket trials aim to identify which tumor types - or baskets - would benefit from the targeted therapy among patients with the same molecular marker or mutation. We propose the implementation of continuous monitoring for basket trials to increase the likelihood of early identification of non-promising baskets. Although the current Bayesian trial designs available in the literature can incorporate more than one interim analysis, most of them have high computational cost, and none of them handle delayed outcomes that are expected for targeted treatments such as immunotherapies. We leverage the Bayesian empirical approach proposed by Fujiwara et al., which has low computational cost. We also extend ideas of Cai et al to address the practical challenge of performing interim analysis with delayed outcomes using multiple imputation. Operating characteristics of four different strategies to handle delayed outcomes in basket trials are compared in an extensive simulation study with the benchmark strategy where trial accrual is put on hold until complete data is observed to make a decision. The optimal handling of missing data at interim analyses is trial-dependent. With slow accrual, missingness is minimal even with continuous monitoring, favoring simpler approaches over computationally intensive methods. Although individual sample-size savings are small, multiple imputation becomes more appealing when sample size savings scale with the number of baskets and agents tested.

翻译：精准医疗已引发范式转变，使得靶向药物的开发不再受限于肿瘤部位。在此背景下，篮式试验旨在确定具有相同分子标志物或突变的患者中，哪些肿瘤类型（或称“篮子”）能从靶向治疗中获益。我们提出在篮式试验中实施连续监测，以提高早期识别无前景篮子的可能性。尽管现有文献中的贝叶斯试验设计可纳入多次期中分析，但大多具有较高的计算成本，且均未处理靶向治疗（如免疫疗法）预期会出现的延迟结局问题。我们采用Fujiwara等人提出的计算成本较低的贝叶斯经验方法，并拓展Cai等人的思路，通过多重插补解决延迟结局下进行期中分析的实际挑战。通过大规模模拟研究，我们将处理篮式试验延迟结局的四种策略与基准策略（即暂停试验入组直至获得完整数据再作决策）进行比较。期中分析中缺失数据处理的最优方案取决于具体试验。在入组缓慢的情况下，即使进行连续监测，缺失数据也极少，此时简单方法比计算密集型方法更具优势。虽然单个样本的样本量节省有限，但当节省的样本量随测试篮子数量和药物种类增加时，多重插补方法将更具吸引力。