Sample size re-estimation: recent developments and practical considerations
Sample size re-estimation: recent developments and practical considerations
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DOI：
10.1002/sim.733
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发表时间：
2001-09-15
影响因子：
2
通讯作者：
Gould, AL
中科院分区：
文献类型：
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作者：
Gould, AL
临床试验的中期结果通常有助于在必要时增加样本量，以便在替代假设为真时提供所需的力量来对抗无效假设。过去几年所描述的进行中期检查的策略包括“内部试点研究”、盲目的临时样本量调整和有条件的权力。仿真研究表明，虽然功率特性变化较大，但这些替代方法一般能令人满意地控制第I类误码率。与样本量重新估计相关的重要问题是战略问题，而不是数字问题。明确表达的监管偏好表明，在试验完成之前不需要对数据进行解盲的方法将是最合适的。延长试验是有风险的。在试验过程中较晚招募的研究人员/患者不一定与较早招募/进入的研究人员/患者相同。重新启动登记程序可能足够复杂和昂贵，足以证明在一开始就招募更多的研究人员/患者是合理的。由于样本量重估计是在变异性的基础上调整样本量，而疗效中期分析是在估计效应量的基础上调整样本量，所以这两个原则都可以在同一试验中使用。对于涉及延长个别患者随访时间的试验，或者更广泛地说，当随访时间相对于招募时间较长时，重新估计样本量可能是不可取的。在这种情况下，保守估计样本量并引入中期疗效评估可能更好。版权所有(C)2001 John Wiley&Sons，Ltd.
Interim findings of a clinical trial often will be useful for increasing the sample size if necessary to provide the required power against the null hypothesis when the alternative hypothesis is true. Strategies for carrying out the interim examination that have been described over the past several years include 'internal pilot studies', blinded interim sample size adjustment and conditional power. Simulation studies show that the alternative methods generally control the type I error rate satisfactorily, although the power properties are more variable. The important issues associated with sample size re-estimation are strategic, not numeric. Clearly expressed regulatory preferences suggest that methods not requiring unblinding the data before completion of the trial would be most appropriate. Extending a trial has its risks. The investigators/patients enrolled later in the course of a trial are not necessarily the same as those recruited/entered early. Re-activating the enrolment process may be sufficiently complicated and expensive to justify enrolling more investigators/patients at the outset. Since sample size re-estimation adjusts the sample size on the basis of variability while efficacy interim analysis adjusts the sample size based on the basis of estimated effect size, both principles can be used in the same trial. Sample size re-estimation may not be advisable for trials involving extended follow-up of individual patients or, more generally, when the follow-up time is long relative to the recruitment time. In such cases, it may be better to estimate the sample size conservatively and introduce an interim efficacy evaluation. Copyright (C) 2001 John Wiley & Sons, Ltd.