Controlling the family-wise error rate in multi-arm, multi-stage trials.

BACKGROUND AND AIMS

Multi-arm, multi-stage trials have recently gained attention as a means to improve the efficiency of the clinical trials process. Many designs have been proposed, but few explicitly consider the inherent issue of multiplicity and the associated type I error rate inflation. It is our aim to propose a straightforward design that controls family-wise error rate while still providing improved efficiency.

METHODS

In this article, we provide an analytical method for calculating the family-wise error rate for a multi-arm, multi-stage trial and highlight the potential for considerable error rate inflation in uncontrolled designs. We propose a simple method to control the error rate that also allows for computation of power and expected sample size.

RESULTS

Family-wise error rate can be controlled in a variety of multi-arm, mutli-stage trial designs using our method. Additionally, our design can substantially decrease the expected sample size of a study while maintaining adequate power.

CONCLUSION

Multi-arm, multi-stage designs have the potential to reduce the time and other resources spent on clinical trials. Our relatively simple design allows this to be achieved while weakly controlling family-wise error rate and without sacrificing much power.