Warwick Medical School, The University of Warwick, Coventry, CV4 7AL, UK.
Stat Med. 2012 Aug 30;31(19):2068-85. doi: 10.1002/sim.5326. Epub 2012 Mar 22.
Hommel (Biometrical Journal; 45:581-589) proposed a flexible testing procedure for seamless phase II/III clinical trials. Schmidli et al. (Statistics in Medicine; 26:4925-4938), Kimani et al. (Statistics in Medicine; 28:917-936) and Brannath et al. (Statistics in Medicine; 28:1445-1463) exploited the flexible testing of Hommel to propose adaptation in seamless phase II/III clinical trials that incorporate prior knowledge by using Bayesian methods. In this paper, we show that adaptation incorporating prior knowledge may lead to higher power. Other important issues to consider in such adaptive designs are the gain in power (or saving in patients) over traditional testing and how utility values used to make the adaptation may be used to stop a trial early. In contrast to the aforementioned authors, we discuss these issues in detail and propose a unified approach to address them so that implementing the aforementioned designs and proposing similar designs is clearer.
霍梅尔（Biometrical Journal；45:581-589）提出了一种用于无缝二期/三期临床试验的灵活测试程序。施密德利等人（Statistics in Medicine；26:4925-4938）、金马尼等人（Statistics in Medicine；28:917-936）和布兰纳特等人（Statistics in Medicine；28:1445-1463）利用霍梅尔的灵活测试方法，通过贝叶斯方法提出了在无缝二期/三期临床试验中利用先验知识进行适应性调整的方法。在本文中，我们表明，包含先验知识的适应性调整可能会导致更高的功效。在这种自适应设计中，还需要考虑其他重要问题，例如与传统测试相比，功效的提高（或患者人数的减少），以及用于进行适应性调整的效用值如何用于提前终止试验。与上述作者不同，我们详细讨论了这些问题，并提出了一种统一的方法来解决这些问题，以便更清楚地实现上述设计和提出类似的设计。
