Chen Michael, Kianifard Farid, Dhar Sunil K
Biometrics, US Clinical Development and Medical Affairs, Novartis Pharmaceuticals, East Hanover, NJ 07936, USA.
J Biopharm Stat. 2006 May;16(3):357-63. doi: 10.1080/10543400600609478.
A randomized, active-control clinical trial setting with the objective of testing noninferiority for a continuous response variable is considered. Noninferiority margin is based on the concept of preserving a certain fraction of the active control effect. Noninferiority is established if the ratio of the lower (upper) limit of the two-sided 95% confidence interval for the treatment difference to the estimated mean of the active control is greater (less) than a certain fraction. The nominal significance level is not maintained by the above confidence interval-based noninferiority test. We use bootstrapping to derive an accurate lower (upper) limit of the same confidence interval, which approximates the nominal significance level better and improves the power.
考虑一种随机、活性对照临床试验设置，其目的是检验连续反应变量的非劣效性。非劣效性界值基于保留活性对照效应的一定比例的概念。如果治疗差异的双侧95%置信区间的下限（上限）与活性对照的估计均值之比大于（小于）某一比例，则确立非劣效性。上述基于置信区间的非劣效性检验不能维持名义显著性水平。我们使用自助法来推导同一置信区间的准确下限（上限），其能更好地逼近名义显著性水平并提高检验效能。
