Sample size re-estimation without unblinding for normally distributed outcomes with unknown variance

Abstract

Monitoring clinical trials in nonfatal diseases where ethical considerations do not dictate early termination upon demonstration of efficacy often requires examining the interim findings to assure that the protocol-specified sample size will provide sufficient power against the null hypothesis when the alternative hypothesis is true. The sample size may be increased, if necessary to assure adequate power. This paper presents a new method for carrying out such interim power evaluations for observations from normal distributions without unblinding the treatment assignments or discernably affecting the Type 1 error rate. Simulation studies confirm the expected performance of the method.

Keywords:

• sample size adjustment
• interim analysis
• clinical trial
• EM algorithm