Increasing the sample size when the unblinded interim result is promising
Increasing the sample size when the unblinded interim result is promising
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DOI：
10.1002/sim.1688
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发表时间：
2004-04-15
影响因子：
2
通讯作者：
Lan, KKG
中科院分区：
文献类型：
--
作者：
Chen, YHJ;DeMets, DL;Lan, KKG
根据非盲中期结果增加样本量可能会增加 I 类错误率，并且可能需要进行适当的统计调整以将 I 类错误率控制在标称水平。我们简要回顾一下现有的方法，这些方法允许由于无效而提前停止，或者通过使用不同的权重来改变测试统计量，或者调整最终测试的临界值，或者强制执行样本量重新计算的规则。讨论了由于无效而提前停止的含义以及对加权 Z 统计方法的简单修改。在本文中，我们表明，当非盲中期结果有希望时增加样本量不会增加 I 类错误率，因此不需要进行统计调整。如果条件功效大于 50% 或等效地，实现所需功效所需的样本量增量不超过上限，则非盲中期结果被认为是有希望的。实际样本量增量可能由预算、合格患者群体规模和市场竞争等重要因素决定。 50％条件功效方法扩展到具有一项中期分析的分组序贯试验，其中可以在中期分析时做出决定，由于令人信服的治疗益处而提前停止试验，或者如果中期结果不如预期则增加样本量。如果仅当条件功效大于 50% 时才可以增加样本量，则 I 类错误率不会被夸大。如果组序贯试验中有两个或多个中期分析，我们的模拟研究表明，I 类错误率也得到了很好的控制。版权所有 (C) 2004 John Wiley Sons, Ltd.
Increasing the sample size based on unblinded interim result may inflate the type I error rate and appropriate statistical adjustments may be needed to control the type I error rate at the nominal level. We briefly review the existing approaches which allow early stopping due to futility, or change the test statistic by using different weights, or adjust the critical value for final test, or enforce rules for sample size recalculation. The implication of early stopping due to futility and a simple modification to the weighted Z-statistic approach are discussed. In this paper, we show that increasing the sample size when the unblinded interim result is promising will not inflate the type I error rate and therefore no statistical adjustment is necessary. The unblinded interim result is considered promising if the conditional power is greater than 50 per cent or equivalently, the sample size increment needed to achieve a desired power does not exceed an upper bound. The actual sample size increment may be determined by important factors such as budget, size of the eligible patient population and competition in the market. The 50 per cent-conditional-power approach is extended to a group sequential trial with one interim analysis where a decision may be made at the interim analysis to stop the trial early due to a convincing treatment benefit, or to increase the sample size if the interim result is not as good as expected. The type I error rate will not be inflated if the sample size may be increased only when the conditional power is greater than 50 per cent. If there are two or more interim analyses in a group sequential trial, our simulation study shows that the type I error rate is also well controlled. Copyright (C) 2004 John Wiley Sons, Ltd.