Prior probabilities of clinical hypotheses are not systematically used for clinical trial design yet, due to a concern that poor priors may lead to poor decisions. To address this concern, a conservative approach to Bayesian trial design is illustrated here, requiring that the operational characteristics of the primary trial outcome are stronger than the prior. This approach is complementary to current Bayesian design methods, in that it insures against prior-data conflict by defining a sample size commensurate to a fixed design prior. This approach is ethical, in that it requires designs appropriate to achieving pre-specified levels of clinical equipoise imbalance. Practical examples are discussed, illustrating design of trials with binary or time to event endpoints. Moderate increases in phase II study sample size are shown to deliver strong levels of overall evidence for go/no-go clinical development decisions. Levels of negative evidence provided by group sequential confirmatory designs are found negligible, highlighting the importance of complementing efficacy boundaries with non-binding futility criteria.

翻译：临床假设的先验概率尚未被系统性用于临床试验设计，原因在于对不当先验可能导致错误决策的担忧。为解决此问题，本文阐述了一种保守的贝叶斯试验设计方法，要求主要试验结局的操作特征强于先验信息。该方法与现有贝叶斯设计方法互为补充，通过定义与固定设计先验相称的样本量来防范先验-数据冲突。该方案符合伦理规范，要求设计能够达到预先设定的临床均势失衡水平。通过讨论二分类结局或时间至事件终点试验的设计实例，表明适度增加II期研究样本量可为临床开发中的“进行/终止”决策提供强有力整体证据。研究发现成组序贯确证性设计提供的阴性证据水平微不足道，凸显了用非约束性无效性标准补充疗效边界的重要性。