Clinical trials : journal of the Society for Clinical Trials
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Despite the best efforts of investigators, problems forcing design changes can occur in clinical trials. Changes are usually relatively minor, but sometimes not. The primary endpoint or analysis may need to be revised, for example. ⋯ Another way of expressing this is that the data used to inform a design change must give no information about the treatment labels. This restriction has implications for limiting the amount of information examined by a committee deciding whether to make design alterations. While nothing can eliminate the pall cast by breaches of protocol, re-randomization tests following blinded and limited data examination go a long way toward amelioration.
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The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs. ⋯ The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial.