Blinded and unblinded internal pilot study designs for clinical trials with count data
Blinded and unblinded internal pilot study designs for clinical trials with count data
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具有计数数据的临床试验的盲法和非盲法内部试点研究设计
DOI：
10.1002/bimj.201200189
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发表时间：
2013
影响因子：
1.7
通讯作者：
Friede T
中科院分区：
文献类型：
--
作者：
Schneider S;Schmidli H;Friede T
内部试点研究是一种流行的设计特征，用于解决因有害参数的模糊信息而导致的样本量计算中的不确定性。尽管它们很受欢迎，但直到最近才提出了用于计数数据试验的盲样本量重新估计方法，并系统地研究了它们的性质。尽管盲目手术受到监管部门的青睐，但由于担心如果在规划中错误指定治疗效果，盲目手术容易产生偏见，实际应用受到一定程度的限制。在这里，我们比较了非盲法和盲法在偏倚、错误率和样本量分布方面的差异。我们发现，这两种程序都保持了期望的权力，非盲化程序略显宽松，而盲化程序的实际显着水平接近名义水平。此外，我们还证明，在假设的治疗效果存在不确定性的情况下，控制事件率的盲估计量与非盲估计量相比是有偏差的，这导致平均样本量的差异有利于非盲化程序。然而，与检测真实但未知的效应所需的样本大小的平均样本大小的偏差相比，这些差异相当小。我们证明，在许多实际相关的情况下，盲化过程引起的样本量的变化比非盲化过程的小得多。这些方法被扩展到使用准似然方法的过度分散计数，并通过复发性多发性硬化症的试验进行了说明。
Internal pilot studies are a popular design feature to address uncertainties in the sample size calculations caused by vague information on nuisance parameters. Despite their popularity, only very recently blinded sample size reestimation procedures for trials with count data were proposed and their properties systematically investigated. Although blinded procedures are favored by regulatory authorities, practical application is somewhat limited by fears that blinded procedures are prone to bias if the treatment effect was misspecified in the planning. Here, we compare unblinded and blinded procedures with respect to bias, error rates, and sample size distribution. We find that both procedures maintain the desired power and that the unblinded procedure is slightly liberal whereas the actual significance level of the blinded procedure is close to the nominal level. Furthermore, we show that in situations where uncertainty about the assumed treatment effect exists, the blinded estimator of the control event rate is biased in contrast to the unblinded estimator, which results in differences in mean sample sizes in favor of the unblinded procedure. However, these differences are rather small compared to the deviations of the mean sample sizes from the sample size required to detect the true, but unknown effect. We demonstrate that the variation of the sample size resulting from the blinded procedure is in many practically relevant situations considerably smaller than the one of the unblinded procedures. The methods are extended to overdispersed counts using a quasi‐likelihood approach and are illustrated by trials in relapsing multiple sclerosis.
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影响因子：
2
作者：
J. Denne;C. Jennison
通讯作者：
J. Denne;C. Jennison
影响因子：
158.5
作者：
Rudick, RA;Stuart, WH;Babu, A
通讯作者：
Babu, A
影响因子：
1.1
作者：
Brannath, Werner;Burger, Hans Ulrich;Wassmer, Gernot
通讯作者：
Wassmer, Gernot
序贯临床试验的中期试验设计审查。
影响因子：
2
作者：
J. Whitehead;A. Whitehead;S. Todd;K. Bolland;M. Sooriyarachchi
通讯作者：
M. Sooriyarachchi
过度分散计数数据盲法样本量重估方法的稳健性
影响因子：
2
作者：
Schneider S;Schmidli H;Friede T
通讯作者：
Friede T