Monotherapy trials: sequential design.

Abstract

In a sequential clinical trial, the accumulating data are subjected to a series of interim analyses, each of which involves a comparison of the treatments under study in respect of the primary efficacy criterion. The trial is stopped as soon as it is evident that one treatment is superior to the other, or that no such difference is going to be found. The stopping rule is devised to ensure that the required significance level and power are achieved and that valid statistical inference can be drawn at the end of the study. The methodology will be presented by means of a case study. This is the SEReNE study, which was completed last year and compared remacemide with carbamazepine in the treatment of newly diagnosed epilepsy. The study employed a double triangular test: an efficient form of sequential design for the comparison of two active treatments. The primary efficacy response was time from randomisation to the first seizure following dose titration. Details will be given of the stopping rule employed, the number of patients forecasted, the progress of the trial and its final analysis. The procedure adopted will be reviewed, and its suitability for future trials assessed.