Group sequential designs enable interim analyses and potential early stopping for efficacy or futility. While these adaptations improve trial efficiency and ethical considerations, they also introduce bias into the adapted analyses. We demonstrate how failing to account for informative interim decisions in the analysis can substantially affect posterior estimates of the treatment effect, often resulting in overly optimistic credible intervals aligned with the stopping decision. Drawing on information theory, we use the Kullback-Leibler divergence to quantify this distortion and highlight its use for post-hoc evaluation of informative interim decisions, with a focus on end-of-study inference. Unlike pointwise comparisons, this measure provides an integrated summary of this distortion on the whole parameter space. By comparing alternative decision boundaries and prior specifications, we illustrate how this measure can improve the understanding of trial results and inform the planning of future adaptive studies. We also introduce an expected version of this metric to support clinicians in choosing decision boundaries. This guidance complements traditional strategies based on type-I error rate control by offering insights into the distortion introduced to the treatment effect at each interim phase. The use of this pre-experimental measure is finally illustrated in a group sequential trial for evaluating a treatment for central nervous system disorders.

翻译：组序贯设计允许进行期中分析，并可能因疗效或无效性而提前终止试验。尽管这些适应性调整提高了试验效率并考虑了伦理因素，但它们也会给适应性分析引入偏倚。我们证明了在分析中未能考虑信息性期中决策会如何显著影响治疗效果的后验估计，通常导致与终止决策一致的过度乐观的可信区间。借鉴信息论，我们使用Kullback-Leibler散度来量化这种扭曲，并重点说明其在研究结束推断中用于信息性期中决策的事后评估。与逐点比较不同，该度量提供了这种扭曲在整个参数空间上的综合概括。通过比较不同的决策边界和先验设定，我们阐述了该度量如何能增进对试验结果的理解，并为未来适应性研究的规划提供信息。我们还引入了该度量的期望版本，以支持临床医生选择决策边界。这一指导通过提供对每个期中阶段引入的治疗效果扭曲的深入理解，补充了基于I类错误率控制的传统策略。最后，我们通过一项评估中枢神经系统疾病治疗的组序贯试验，说明了这一预实验度量的应用。