[Application of sequential methods in randomized clinical trials with censored response criteria]

In randomized clinical trials with a censored response criterion, it is common practice to perform interim analyses, especially for reasons of medical ethics. Sequential methods allow for repeated testing. Three sequential methods are well adapted to censored data: the group sequential analysis, the sequential probability ratio test and the triangular test. Among them, the triangular test has the best statistical properties. The influence of the frequency of the analyses on the statistical properties of sequential methods has been studied by simulation: sequential analyses need not be performed more frequently than interim analyses. Sequential methods have been applied to several randomized clinical trials. The results are briefly reported for two of them. The ability of the triangular test and of the sequential probability ratio test to reach conclusions early when there is no difference between two compared treatments is supported by these two examples. Moreover, careful patient follow-up must be planned in the protocol in order to reduce the time for data updating and to perform sequential analyses at the required frequency. It appears well-founded to propose the use of the triangular test in randomized clinical trials with a censored response criterion. Four types of analyses with different aims must be planned in the protocol.