Drop-the-Losers Design: Normal Case

Drop‐the‐losers designs are statistical designs which have two stages of a trial separated by a data based decision. In the first stage k experimental treatments and a control are administered. During a transition period, the empirically best experimental treatment is selected for continuation into the second phase, along with the control. At the study's end, inference focuses on the comparison of the selected treatment with the control using both stages' data. Traditional methods used to make inferences based on both stages' data can yield tests with higher than advertised levels of significance and confidence intervals with lower than advertised confidence. For normally distributed data, methods are provided to correct these deficiencies, providing confidence intervals with accurate levels of confidence. Drop‐the‐losers designs are particularly applicable to biopharmaceutical clinical trials where they can allow Phase II and Phase III clinical trials to be conducted under a single protocol with the use of all available data. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)