For a Phase III randomized trial that compares survival outcomes between an experimental treatment versus a standard therapy, interim monitoring analysis is used to potentially terminate the study early based on efficacy. To preserve the nominal Type I error rate, alpha spending methods and information fractions are used to compute appropriate rejection boundaries in studies with planned interim analyses. For a one-sided trial design applied to a scenario in which the experimental therapy is superior to the standard therapy, interim monitoring should provide the opportunity to stop the trial prior to full follow-up and conclude that the experimental therapy is superior. This paper proposes a method called total control only (TCO) for estimating the information fraction based on the number of events within the standard treatment regimen. Based on theoretical derivations and simulation studies, for a maximum duration superiority design, the TCO method is not influenced by departure from the designed hazard ratio, is sensitive to detecting treatment differences, and preserves the Type I error rate compared to information fraction estimation methods that are based on total observed events. The TCO method is simple to apply, provides unbiased estimates of the information fraction, and does not rely on statistical assumptions that are impossible to verify at the design stage. For these reasons, the TCO method is a good approach when designing a maximum duration superiority trial with planned interim monitoring analyses.

中文翻译：

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基于标准治疗方案内事件数量的信息分数估计

对于比较实验性治疗与标准治疗之间的生存结果的 III 期随机试验，中期监测分析用于根据疗效提前终止研究。为了保持名义上的 I 类错误率，在计划的中期分析的研究中，使用 alpha 花费方法和信息分数来计算适当的拒绝边界。对于应用于实验疗法优于标准疗法的情况的单方面试验设计，中期监测应提供在全面随访之前停止试验并得出实验疗法优于标准疗法的结论的机会。本文提出了一种称为仅完全控制（TCO）的方法，用于根据标准治疗方案内的事件数量估计信息分数。基于理论推导和模拟研究，对于最大持续时间优势设计，TCO 方法不受偏离设计风险比的影响，对检测治疗差异敏感，并且与信息分数估计方法相比保留了 I 类错误率基于观察到的事件总数。TCO 方法应用简单，提供信息分数的无偏估计，并且不依赖于在设计阶段无法验证的统计假设。由于这些原因，在设计具有计划的中期监测分析的最大持续时间优效性试验时，TCO 方法是一种很好的方法。