Clinical trials are an instrument for making informed decisions based on evidence from well-designed experiments. Here we consider adaptive designs mainly from the perspective of multi-arm Phase II clinical trials, in which one or more experimental treatments are compared to a control. Treatment allocation of individual trial participants is assumed to take place according to a fixed block randomization, albeit with an important twist: The performance of each treatment arm is assessed after every measured outcome, in terms of the posterior distribution of a corresponding model parameter. Different treatments arms are then compared to each other, according to pre-defined criteria and using the joint posterior as the basis for such assessment. If a treatment is found to be sufficiently clearly inferior to the currently best candidate, it can be closed off either temporarily or permanently from further participant accrual. The latter possibility provides a method for adaptive treatment selection, including early stopping of the trial. The main development in the paper is in terms of binary outcomes, but some extensions, notably for handling time-to-event data, are discussed as well. The presentation is to a large extent comparative and expository.
翻译:临床试验是依据精心设计的实验证据作出知情决定的工具。我们在这里主要从多种武器第二阶段临床试验的角度考虑适应性设计,其中将一种或多种实验治疗与控制相提并论。假定个别试验参与者的治疗分配按固定的区块随机安排进行,尽管有很大的曲折:每个治疗臂的性能在每个测结果之后,根据相应模型参数的后表分布,根据每个处理臂的性能进行评估。然后根据预先确定的标准,用联合后表作为评估的基础,对不同的处理臂进行比较。如果发现治疗明显低于目前的最佳候选者,则可以暂时或永久停止治疗。后一可能性是适应性治疗选择的方法,包括及早停止试验。文件的主要发展是在二进制结果方面,但也讨论一些扩展,特别是处理时间-事件数据方面的一些扩展。介绍在很大程度上是比较和解释性的。