Hartung Joachim
Department of Statistics, University of Dortmund, 44221 Dortmund, Germany.
Biom J. 2006 Aug;48(4):521-36. doi: 10.1002/bimj.200510212.
Flexible designs are provided by adaptive planning of sample sizes as well as by introducing the weighted inverse normal combining method and the generalized inverse chi-square combining method in the context of conducting trials consecutively step by step. These general combining methods allow quite different weighting of sequential study parts, also in a completely adaptive way, based on full information from unblinded data in previously performed stages. So, in reviewing some basic developments of flexible designing, we consider a generalizing approach to group sequentially performed clinical trials of Pocock-type, of O'Brien-Fleming-type, and of Self-designing-type. A clinical trial may be originally planned either to show non-inferiority or superiority. The proposed flexible designs, however, allow in each interim analysis to change the planning from showing non-inferiority to showing superiority and vice versa. Several examples of clinical trials with normal and binary outcomes are worked out in detail. We demonstrate the practicable performance of the discussed approaches, confirmed in an extensive simulation study. Our flexible designing is a useful tool, provided that a priori information about parameters involved in the trial is not available or subject to uncertainty.
灵活设计通过样本量的自适应规划以及在逐步连续进行试验的背景下引入加权逆正态合并方法和广义逆卡方合并方法来实现。这些通用合并方法允许基于先前阶段未盲法数据的完整信息，以完全自适应的方式对连续研究部分进行截然不同的加权。因此，在回顾灵活设计的一些基本发展时，我们考虑一种对Pocock型、O'Brien-Fleming型和自我设计型的序贯分组进行的临床试验进行推广的方法。一项临床试验最初可能计划显示非劣效性或优越性。然而，所提出的灵活设计允许在每次中期分析中从显示非劣效性转变为显示优越性，反之亦然。详细给出了一些具有正态和二元结果的临床试验示例。我们展示了所讨论方法的实际性能，这在广泛的模拟研究中得到了证实。我们的灵活设计是一个有用的工具，前提是关于试验中涉及参数的先验信息不可用或存在不确定性。
