A method to estimate the variance of an endpoint from an on-going blinded trial

Blinded estimation of variance allows for changing the sample size without compromising the integrity of the trial. Some of the methods that estimate the variance in a blinded manner either make untenable assumptions or are only applicable to two-treatment trials. We propose a new method for continuous endpoints that makes minimal assumptions. The method uses the enrollment order of subjects and the randomization block size to estimate the variance. It can be applied to normal or non-normal data, trials with two or more treatments, equal or unequal allocation schemes, fixed or random randomization block sizes, and single or multi-centre trials. The variance estimator is unbiased and performs best when the randomization block size is the smallest. Simulation results suggest that for many commonly used randomization block sizes the proposed estimator is expected to perform well. The proposed method is used to estimate the variance of the endpoint for two trials and is shown to perform well by comparison with its unblinded counterpart. Copyright (c) 2005 John Wiley & Sons, Ltd.