Berry D A, Pearson L M
Stat Med. 1985 Oct-Dec;4(4):497-508. doi: 10.1002/sim.4780040410.
We consider two-stage designs for clinical trials that involve two treatments with dichotomous responses. The first is the information-gathering stage; the treatment chosen as the better from first stage and prior data is used exclusively in the second stage. Determination of treatment allocation in the first stage results from weighing the anticipated gain in information with effective treatment; the objective is to maximize the expected number of successes in the entire trial. This is in contrast to randomized controlled trials with the restricted objective of obtaining information concerning treatment differences. We allow the length of the first stage to be arbitrary and fixed in advance, or optimized as a function of prior information and the 'patient horizon'. We can regard this patient horizon as either the number of patients in the trial or the number who have the condition under treatment. We consider two forms of prior information: both success probabilities known but the better of the two treatments is unknown, and one success probability known whereas the other has an arbitrary distribution. In many instances of the latter case the optimal first stage size is of the order of the square root of the patient horizon.
我们考虑用于涉及两种具有二分反应治疗方法的临床试验的两阶段设计。第一阶段是信息收集阶段；从第一阶段和先前数据中被选为更好的治疗方法仅在第二阶段使用。第一阶段治疗分配的确定是通过权衡有效治疗中预期的信息增益来实现的；目标是使整个试验中的成功预期数量最大化。这与旨在获取有关治疗差异信息这一受限目标的随机对照试验形成对比。我们允许第一阶段的长度是任意的且提前固定，或者根据先验信息和“患者范围”进行优化。我们可以将这个患者范围视为试验中的患者数量或患有正在接受治疗疾病的患者数量。我们考虑两种先验信息形式：两种成功概率已知但两种治疗方法中更好的未知，以及一种成功概率已知而另一种具有任意分布。在后一种情况的许多实例中，最优的第一阶段规模约为患者范围的平方根。
