论文标题
篮子试验有限混合模型的混合物
Mixture of Finite Mixtures Model for Basket Trial
论文作者
论文摘要
随着最近从细胞毒性药物转变为肿瘤药物开发期间新一代靶向治疗和免疫肿瘤治疗的新一代,如果具有相同的分子靶标,患有各种癌症(SUB)类型的患者可能有资格参加篮子试验。贝叶斯分层建模(BHM)被广泛用于篮子试验数据分析中,它们可以在不同的队列(亚型)之间适应信息,而不是基于每个队列进行分层分析。但是,由于无效的可交换假设,这些方法可能有过度收缩估计的风险。我们提出了一个两步程序,以找到合并分析和分层分析之间的平衡。在第一步中,我们通过将同类人群分组为具有相似治疗效果的簇,将其视为聚类问题。在第二步中,我们使用从BHM的收缩估计量来估计可交换假设下每个群集中队列的治疗效果。对于聚类部分,我们适应有限混合物(MFM)方法的混合物,以一致地估计簇数。我们研究了我们提出的方法在仿真研究中的性能,并将这种方法应用于Vemurafenib篮子试验数据分析。
With the recent paradigm shift from cytotoxic drugs to new generation of target therapy and immuno-oncology therapy during oncology drug developments, patients with various cancer (sub)types may be eligible to participate in a basket trial if they have the same molecular target. Bayesian hierarchical modeling (BHM) are widely used in basket trial data analysis, where they adaptively borrow information among different cohorts (subtypes) rather than fully pool the data together or doing stratified analysis based on each cohort. Those approaches, however, may have the risk of over shrinkage estimation because of the invalidated exchangeable assumption. We propose a two-step procedure to find the balance between pooled and stratified analysis. In the first step, we treat it as a clustering problem by grouping cohorts into clusters that share the similar treatment effect. In the second step, we use shrinkage estimator from BHM to estimate treatment effects for cohorts within each cluster under exchangeable assumption. For clustering part, we adapt the mixture of finite mixtures (MFM) approach to have consistent estimate of the number of clusters. We investigate the performance of our proposed method in simulation studies and apply this method to Vemurafenib basket trial data analysis.