A bootstrap-based test for establishing noninferiority in clinical trials.
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.
Chen
Michael
M
Biometrics, US Clinical Development and Medical Affairs, Novartis Pharmaceuticals, East Hanover, NJ 07936, USA.
Kianifard
Farid
F
Dhar
Sunil K
SK
D003198:Computer Simulation; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design