Friede Tim, Stallard Nigel
Warwick Medical School, The University of Warwick, Coventry CV47AL, United Kingdom.
Biom J. 2008 Oct;50(5):767-81. doi: 10.1002/bimj.200710453.
Traditionally drug development is generally divided into three phases which have different aims and objectives. Recently so-called adaptive seamless designs that allow combination of the objectives of different development phases into a single trial have gained much interest. Adaptive trials combining treatment selection typical for Phase II and confirmation of efficacy as in Phase III are referred to as adaptive seamless Phase II/III designs and are considered in this paper. We compared four methods for adaptive treatment selection, namely the classical Dunnett test, an adaptive version of the Dunnett test based on the conditional error approach, the combination test approach, and an approach within the classical group-sequential framework. The latter two approaches have only recently been published. In a simulation study we found that no one method dominates the others in terms of power apart from the adaptive Dunnett test that dominates the classical Dunnett by construction. Furthermore, scenarios under which one approach outperforms others are described.
传统上，药物研发一般分为三个阶段，每个阶段有不同的目的和目标。最近，所谓的适应性无缝设计允许将不同研发阶段的目标合并到一个单一试验中，这种设计引起了广泛关注。将II期典型的治疗选择与III期的疗效确认相结合的适应性试验被称为适应性无缝II/III期设计，本文将对此进行探讨。我们比较了四种适应性治疗选择方法，即经典的Dunnett检验、基于条件误差方法的Dunnett检验的适应性版本、联合检验方法以及经典组序贯框架内的一种方法。后两种方法最近才发表。在一项模拟研究中，我们发现，除了基于构建方式优于经典Dunnett检验的适应性Dunnett检验外，没有一种方法在检验效能方面优于其他方法。此外，还描述了一种方法优于其他方法的情形。
