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Abstract:
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Clinical trials with adaptive sample size re-assessment, based on an unblinded interim analysis (ubSSR), have gained in popularity due to uncertainty in the treatment effect 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. We present a methodology for making this efficiency comparison in an objective manner by plotting the unconditional power curves of the two approaches while holding constant their expected sample size, at each value of the treatment effect in the range of interest. Under reasonable 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. The proposed methodology helps one evaluate whether the efficiency loss, if any, of a ubSSR design relative to a comparable group sequential design is offset by the advantages it confers for re-powering the study at the interim analysis.
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