Schoenfeld David A, Cudkowicz Merit
Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts 02115, USA.
Amyotroph Lateral Scler. 2008;9(1):16-23. doi: 10.1080/17482960701875896.
Several important design issues for clinical trials in ALS were presented at the World Federation of Neurology conference at the International Motor Neuron Disease meeting in Yokahama, Japan. We present a discussion, and critique, of the important ideas that were presented with regard to phase II trials. In particular we critique the use of 'Futility Designs' because, as presented at the meeting they will too often lead to the testing of ineffective drugs. We show that except under a highly restrictive model, the use of a 'Lead In' period has only a minor effect on trial efficiency. We show the advantage of using multi-drug phase II trials to select drugs for further study and the advantage of studies that combine phase II and III. We also describe how group sequential trials can be used to stop trials early.
在日本横滨举行的国际运动神经元病会议上，世界神经病学联合会会议提出了肌萎缩侧索硬化症（ALS）临床试验的几个重要设计问题。我们对与II期试验相关的重要观点进行了讨论和批判。特别是，我们批判了“无效性设计”的使用，因为在会议上提出的这种设计往往会导致对无效药物进行测试。我们表明，除了在高度受限的模型下，“导入期”的使用对试验效率只有微小影响。我们展示了使用多药II期试验来选择进一步研究药物的优势以及将II期和III期相结合的研究的优势。我们还描述了如何使用序贯试验提前终止试验。
