Online Program

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Tuesday, September 26
Tue, Sep 26, 4:15 PM - 5:30 PM
Thurgood Marshall South
Parallel Session: Different Approaches to the Increase of a Sample Size When the Unblinded Interim Estimate of the Treatment Effect Looks Promising

Efficiency Considerations for Group Sequential Designs with Adaptive Unblinded Sample Size Re-Assessment (300532)

*Cyrus Mehta, Cytel, Inc. 

Clinical trials with adaptive sample size re-assessment, based on an analysis of the unblinded interim results (ubSSR), have gained in popularity due to uncertainty regarding the value of ? at which to power the trial at the start of the study. While the statistical methodology for controlling the type 1 error of such designs is well established there remain concerns that conventional group sequential designs with no ubSSR can accomplish the same goals with greater efficiency. The precise manner in which this efficiency comparison can be objectified has been difficult to quantify, however. In this paper we present a methodology for making this comparison in an objective manner. It is seen that under reasonable decision rules for increasing sample size there is little or no loss of efficiency for the adaptive designs in terms of unconditional power. The two approaches, however, have very different conditional power profiles. More generally a methodolgy has been provided for comparing any design with ubSSR relative to a comparable group sequential design with no ubSSR, so one can determine whether the efficiency loss, if any, of the ubSSR design is offset by the advantages it confers for re-powering the study at the time of the interim analysis.