Choose a group sequential design. Randomize patients among the three arms, schedule interim analyses after prespecified amounts of information, and calculate the two Wald test statistics at each look. Prespecify efficacy boundaries and a futility rule; allow early stopping of an ineffective experimental arm or of the trial when sufficiently convincing efficacy evidence is obtained. Calibrate the boundaries for both repeated looks and the two shared-control comparisons so that the familywise error rate remains controlled. An alpha-spending function is one way to allocate the error probability across looks.
Two potential benefits are lower expected recruitment and shorter duration when a treatment is clearly effective or futile, and earlier identification of benefit or lack of benefit, reducing continued exposure to an ineffective experimental treatment. These benefits concern expected performance; the maximum sample size may still be required.
Two drawbacks are the extra operational work needed for rapid, reliable outcomes and confidential interim analyses, and more complicated inference: repeated testing requires adjusted boundaries, and ordinary fixed-sample effect estimates and confidence intervals can be misleading after data-dependent stopping. Continuing two comparisons against a shared control also requires care if an arm is stopped.
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