Phase II basket trials are popular tools to evaluate efficacy of a new treatment targeting genetic alteration common to a set of different cancer histologies. Efficient designs are obtained by pooling data from the different arms (e.g., cancer histologies) via Bayesian hierarchical modelling, with a variance parameter controlling the strength of shrinkage of each arm treatment effect to the overall treatment effect. One critical aspect of this approach is that prior choice on the variance plays a major role in determining the strength of shrinkage and impacts the operating characteristics of the design. We review the priors most commonly adopted in previous works and compare them with the recently introduced penalized complexity (PC) priors. Our simulation study shows comparable behaviour for the PC prior and the gold standard choice half-t prior, with the former performing better in the homogeneous scenario where all histologies respond similarly to the treatment. We argue that PC priors offer advantages over other priors because they allow the user to handle the degree of shrinkage by means of only one parameter and can be elicited based on clinical opinion when available.
翻译:第二阶段的篮子试验是评价针对一系列不同癌症遗传学的常见基因改变的新治疗效果的流行工具,通过巴耶西亚等级建模将不同手臂的数据(例如癌症基因学)汇集在一起,从而获得高效的设计,同时有一个差异参数控制着每个手臂治疗效果的缩缩缩强度与总体治疗效果。这一方法的一个重要方面是,对差异的事先选择在确定缩缩缩强度和影响设计操作特征方面起着重要作用。我们审查了以往工作中最常用的前科,并将其与最近采用的受处罚复杂性(PC)前科进行比较。我们的模拟研究显示,个人计算机前科和黄金标准选择前半前科的类似行为,前者在同质假设中表现得更好,而所有类型都对治疗作出类似反应。我们认为,个人计算机前科具有优势,因为它们只允许用户用一个参数处理缩缩小程度,并在具备临床意见时根据临床意见进行查询。