A new conditional performance score for the evaluation of adaptive group sequential designs with sample size recalculation
A new conditional performance score for the evaluation of adaptive group sequential designs with sample size recalculation
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DOI：
10.1002/sim.8534
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发表时间：
2020-07-10
影响因子：
2
通讯作者：
Rauch, Geraldine
中科院分区：
文献类型：
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作者：
Herrmann, Carolin;Pilz, Maximilian;Rauch, Geraldine
在标准的临床试验设计中，根据初始参数假设，在计划阶段确定所需的样本量。根据直觉，正确选择样本量对试验的伦理合理性至关重要。所需的参数假设应基于先前发表的文献结果。然而，在临床实践中，历史数据往往不存在或显示高度可变的结果。自适应组序贯设计允许在计划的非盲期中分析后重新计算样本量，以便在正在进行的试验中调整样本量。到目前为止，还没有统一的标准来评价样本量重算规则的执行情况。通常报告的单一性能标准是由功率和平均样本量给出的；重新计算的样本量和条件功率分布的可变性通常被忽略。因此，显然需要结合这些相关性能标准的适当性能评分。要判断自适应设计的性能，存在两种可能的视角，它们也可以组合在一起：可以处理设计的全局性能，即对所有可能的中期结果进行平均处理，或者处理条件性能，其重点放在以特定中期结果为条件的剩余性能上。在这项工作中，我们给出了样本大小重新计算规则和性能措施的紧凑概述。此外，我们提出了一种新的条件性能评分，并通过蒙特卡罗模拟将其应用于各种标准重计算规则。
In standard clinical trial designs, the required sample size is fixed in the planning stage based on initial parameter assumptions. It is intuitive that the correct choice of the sample size is of major importance for an ethical justification of the trial. The required parameter assumptions should be based on previously published results from the literature. In clinical practice, however, historical data often do not exist or show highly variable results. Adaptive group sequential designs allow a sample size recalculation after a planned unblinded interim analysis in order to adjust the sample size during the ongoing trial. So far, there exist no unique standards to assess the performance of sample size recalculation rules. Single performance criteria commonly reported are given by the power and the average sample size; the variability of the recalculated sample size and the conditional power distribution are usually ignored. Therefore, the need for an adequate performance score combining these relevant performance criteria is evident. To judge the performance of an adaptive design, there exist two possible perspectives, which might also be combined: Either the global performance of the design can be addressed, which averages over all possible interim results, or the conditional performance is addressed, which focuses on the remaining performance conditional on a specific interim result. In this work, we give a compact overview of sample size recalculation rules and performance measures. Moreover, we propose a new conditional performance score and apply it to various standard recalculation rules by means of Monte-Carlo simulations.