An Example of an Unblinded,Third-Party Interim Analysis for Sample Size Re-Estimation

Abstract

An interim analysis for sample size re-estimation is often carried out in a clinical trial when there is concern about the uncertainty of the estimate of variability used for the prestudy sample size estimation. The use of an unblinded third party to do the interim analysis instead of conventional blinded methods may be possible and may lead to the desired power for the study being more likely to be achieved. An example of a clinical trial where the unblinded, third-party approach was used is described. For the interim results obtained, the decision not to increase the sample size would also have been reached had the project team used either of two commonly adopted blinded sample size re-estimation methods. However, simulation results from some plausible alternative scenarios based on the example show that an unblinded, third-party interim analysis for sample size re-estimation can provide more accurate results than the two blinded methods.