Hirotsu Chihiro
Faculty of Science and Technology, Meisei University, Hodokubo, Hino-city, Tokyo, Japan.
Pharm Stat. 2007 Jul-Sep;6(3):193-203. doi: 10.1002/pst.305.
Two approaches of multiple decision processes are proposed for unifying the non-inferiority, equivalence and superiority tests in a comparative clinical trial for a new drug against an active control. One is a method of confidence set with confidence coefficient 0.95 improving the conventional 0.95 confidence interval in the producer's risk and also the consumer's risk in some cases. It requires to include 0 within the region as well as to clear the non-inferiority margin so that a trial with somewhat large number of subjects and inappropriately large non-inferiority margin for proving non-inferiority of a drug that is actually inferior should be unsuccessful. The other is the closed testing procedure which combines the one- and two-sided tests by applying the partitioning principle and justifies the switching procedure by unifying the non-inferiority, equivalence and superiority tests. In particular regarding the non-inferiority, the proposed method justifies simultaneously the old Japanese Statistical Guideline (one-sided 0.05 test) and the International Guideline ICH E9 (one-sided 0.025 test). The method is particularly attractive, changing the strength of the evidence of relative efficacy of the test drug against a control at five levels according to the achievement of the clinical trial. The meaning of the non-inferiority test and also the rationale of switching from it to superiority test will be discussed.
针对一种新药与活性对照药的比较临床试验，提出了两种多决策过程方法，以统一非劣效性、等效性和优效性检验。一种是置信系数为0.95的置信集方法，它在生产者风险方面改进了传统的0.95置信区间，在某些情况下也改进了消费者风险。它要求在区域内包含0并且明确非劣效界值，这样对于实际上疗效较差的药物，若用数量较多的受试者且采用不适当大的非劣效界值来证明其非劣效性的试验应该是不成功的。另一种是封闭检验程序，它通过应用划分原则将单侧检验和双侧检验结合起来，并通过统一非劣效性、等效性和优效性检验来证明转换程序的合理性。特别是关于非劣效性，所提出的方法同时证明了旧的日本统计指南（单侧0.05检验）和国际指南ICH E9（单侧0.025检验）的合理性。该方法特别有吸引力，它根据临床试验的结果在五个水平上改变了试验药物相对于对照药的相对疗效证据的强度。将讨论非劣效性检验的意义以及从非劣效性检验转换为优效性检验的基本原理。
