Section of Medical Statistics, Core Unit for Medical Statistics and Informatics, Medical University of Vienna, Vienna, Austria.
Stat Med. 2010 Jan 15;29(1):1-13. doi: 10.1002/sim.3716.
We consider the situation where in a first stage of a clinical trial several treatments are compared with a single control and the 'best' treatment(s) are selected in an interim analysis to be carried on to the second stage. We quantify the mean bias and mean square error of the conventional estimates after selection depending on the number of treatments and the selection time during the trial. The cases without or with reshuffling the planned sample size of the dropped treatments to the selected ones are investigated. The mean bias shows very different patterns depending on the selection rule and the unknown parameter values. We stress the fact that the quantification of the bias is possible only in designs with planned adaptivity where the design allows reacting to new evidence, but the decision rules are laid down in advance. Finally, we calculate the mean bias which arises in a simple but influential regulatory selection rule, to register a new medical therapy only when two pivotal trials have both proven an effect by a statistical test.
我们考虑这样一种情况，在临床试验的第一阶段，几种治疗方法与单一对照进行比较，并在中期分析中选择“最佳”治疗方法继续进行第二阶段。我们根据治疗方法的数量和试验期间的选择时间，量化了选择后的常规估计的平均偏差和均方误差。研究了不进行或对已停止治疗的计划样本大小进行重新分配到已选择的治疗方法的情况。平均偏差取决于选择规则和未知参数值，呈现出非常不同的模式。我们强调这样一个事实，即只有在具有计划适应性的设计中才能进行偏差的量化，这种设计允许对新证据做出反应，但决策规则是预先制定的。最后，我们计算了在一种简单但有影响力的监管选择规则中出现的平均偏差，只有当两个关键试验都通过统计检验证明了一种治疗方法有效时，才会注册一种新的医学疗法。
