A re-randomisation design for clinical trials
A re-randomisation design for clinical trials
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DOI：
10.1186/s12874-015-0082-2
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发表时间：
2015-11-05
影响因子：
4
通讯作者：
Morris, Tim P.
中科院分区：
文献类型：
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作者：
Kahan, Brennan C.;Forbes, Andrew B.;Morris, Tim P.
背景：临床试验的招募通常是有问题的，许多试验未能招募到目标样本量。因此，患者护理可能基于不充分的试验或非随机研究的次优证据。方法：对于许多情况，患者将需要多次治疗，例如，治疗潜在的慢性疾病的症状(如偏头痛，每次发生新的发作都需要治疗)，或直到他们取得治疗成功(如生育，患者在怀孕前接受多次治疗)。我们描述了一种针对这些情况的重新随机化设计，它允许每个患者在多次情况下独立随机。结果：在以下情况下，重新随机化设计将给出治疗效果和纠正第I类错误率的渐近无偏估计：(A)患者仅在其先前随机化的随机化完成后才被重新随机化；(B)针对同一患者的随机化是独立进行的；以及(C)在所有随机化中，治疗效果是恒定的。如果分析考虑了来自同一患者的观察之间的相关性，这种设计通常比具有相同观察次数的平行分组试验具有更高的威力。结论：如果使用得当，重新随机设计可以增加临床试验的征集率，同时仍然提供对治疗效果和纠正I型错误率的公正估计。在许多情况下，与具有相同观察次数的平行组设计相比，它可以增加功率。
Background: Recruitment to clinical trials is often problematic, with many trials failing to recruit to their target sample size. As a result, patient care may be based on suboptimal evidence from underpowered trials or non-randomised studies.Methods: For many conditions patients will require treatment on several occasions, for example, to treat symptoms of an underlying chronic condition (such as migraines, where treatment is required each time a new episode occurs), or until they achieve treatment success (such as fertility, where patients undergo treatment on multiple occasions until they become pregnant). We describe a re-randomisation design for these scenarios, which allows each patient to be independently randomised on multiple occasions. We discuss the circumstances in which this design can be used.Results: The re-randomisation design will give asymptotically unbiased estimates of treatment effect and correct type I error rates under the following conditions: (a) patients are only re-randomised after the follow-up period from their previous randomisation is complete; (b) randomisations for the same patient are performed independently; and (c) the treatment effect is constant across all randomisations. Provided the analysis accounts for correlation between observations from the same patient, this design will typically have higher power than a parallel group trial with an equivalent number of observations.Conclusions: If used appropriately, the re-randomisation design can increase the recruitment rate for clinical trials while still providing an unbiased estimate of treatment effect and correct type I error rates. In many situations, it can increase the power compared to a parallel group design with an equivalent number of observations.