Making all pairwise comparisons in multi-arm clinical trials without control treatment

The standard paradigm for confirmatory clinical trials is to compare experimental treatments with a control, for example, the standard of care or a placebo. However, it is not always the case that a suitable control exists. Efficient statistical methodology is well studied in the setting of randomized controlled trials. This is not the case if one wishes to compare several experimental treatments with no control arm. We propose hypothesis testing methods suitable for use in such a setting. These methods are efficient, ensuring the error rate is controlled at exactly the desired rate with no conservatism. This in turn yields an improvement in power when compared with standard methods one might otherwise consider using, such as a Bonferroni adjustment. The proposed testing procedure is also highly flexible. We show how it may be extended for use in multistage adaptive trials, covering the majority of scenarios in which one might consider the use of such procedures in the clinical trials setting. With such a highly flexible nature, these methods may also be applied more broadly outside of a clinical trials setting.