论文标题
保守的方法来利用外部证据进行有效的临床试验设计
A Conservative Approach to Leveraging External Evidence for Effective Clinical Trial Design
论文作者
论文摘要
临床假设的先前概率尚未系统地用于临床试验设计，因为担心先生可能会导致决定不良的问题。为了解决这一问题，这里说明了一种保守的贝叶斯试验设计方法，要求主要试验结果的操作特征比以前更强。这种方法与当前的贝叶斯设计方法是互补的，因为它通过定义与离散设计的样本量来确保对先前数据冲突的确保。这种方法是道德的，因为它需要设计适当的设计，以实现预先指定的临床设备不平衡水平。讨论了实践示例，说明了用二进制或时间端点的时间设计的试验设计。证明II期研究样本量中等增加，可以为GO/NO-GO临床开发决策提供大量的总体证据。群体顺序确认设计提供的负面证据水平可以忽略不计，这突显了与非约束性徒劳标准相辅相成的重要性。
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 discrete 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.
